Ion Transport across Biological Membranes by Carborane-Capped Gold Nanoparticles
- Marcin P. Grzelczak
- ,
- Stephen P. Danks
- ,
- Robert C. Klipp
- ,
- Domagoj Belic
- ,
- Adnana Zaulet
- ,
- Casper Kunstmann-Olsen
- ,
- Dan F. Bradley
- ,
- Tatsuya Tsukuda
- ,
- Clara Viñas
- ,
- Francesc Teixidor
- ,
- Jonathan J. Abramson
- , and
- Mathias Brust
View Author Information
† Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, United Kingdom
‡ Institut de Ciencia de Materials de Barcelona, ICMAB-CSIC, Campus UAB, E-08193 Bellaterra, Spain
§ Physics Department, Portland State University, Portland, Oregon 97207, United States
∥ Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
*E-mail: [email protected]
*E-mail: [email protected]
Copyright © 2017 American Chemical Society
ACS AuthorChoicewith CC-BYlicense
Abstract
Carborane-capped gold nanoparticles (Au/carborane NPs, 2–3 nm) can act as artificial ion transporters across biological membranes. The particles themselves are large hydrophobic anions that have the ability to disperse in aqueous media and to partition over both sides of a phospholipid bilayer membrane. Their presence therefore causes a membrane potential that is determined by the relative concentrations of particles on each side of the membrane according to the Nernst equation. The particles tend to adsorb to both sides of the membrane and can flip across if changes in membrane potential require their repartitioning. Such changes can be made either with a potentiostat in an electrochemical cell or by competition with another partitioning ion, for example, potassium in the presence of its specific transporter valinomycin. Carborane-capped gold nanoparticles have a ligand shell full of voids, which stem from the packing of near spherical ligands on a near spherical metal core. These voids are normally filled with sodium or potassium ions, and the charge is overcompensated by excess electrons in the metal core. The anionic particles are therefore able to take up and release a certain payload of cations and to adjust their net charge accordingly. It is demonstrated by potential-dependent fluorescence spectroscopy that polarized phospholipid membranes of vesicles can be depolarized by ion transport mediated by the particles. It is also shown that the particles act as alkali-ion-specific transporters across free-standing membranes under potentiostatic control. Magnesium ions are not transported.
Ion transport across biological membranes is a fundamental phenomenon ubiquitous in nature. (1-6) Photosynthesis, the respiratory chain, ATP production, muscle contraction, neuronal signaling, and many other key biological processes depend on it. (7, 8) Numerous active and passive transport mechanisms exist ranging from simple ion channels to highly complex and regulated energy-converting nanomachineries. Naturally occurring ion transporters are proteins, whereas artificial ones can be made in different ways, usually from peptides, (9) macrocyclic organic compounds, (10, 11) or appropriately functionalized polymers including DNA. (12-15) Substances that affect ion transport or its regulation play important roles in both basic research and drug development. Carborane-capped gold nanoparticles (16) in the 1–4 nm size range are known for their ability to store and release cationic charge that is counterbalanced by excess electrons in the metal core. (17) This is possible due to the inevitable voids in the ligand shell, which are caused by the near spherical shape of the carborane ligand. It may also be assisted by the dipole moment of the ligand, which in this case is pointing toward the gold surface. Carboranes have the interesting property that the orientation of their dipole moment relative to a surface can be controlled by the position of the two vicinal carbon atoms. (18) Gold nanoparticles loaded up with cations readily disperse in water as net polyanions but, if possible, tend to associate with water/oil interfaces or with hydrophobic membranes. Unlike most other nanoscopic forms of gold, (19) the particles are cytotoxic and can enter biological cells by direct membrane penetration and finally lodge inside membranous structures including the mitochondria. Here, we report that 2–3 nm gold nanoparticles protected by mercaptocarborane ligands (a) readily penetrate phospholipid bilayer membranes and establish a membrane potential as partitioning anions and (b) effect the transport of alkali cations across the membrane and hence represent a class of membrane transporters. Two complementary experimental techniques have been used to study these phenomena: (i) voltage-dependent fluorescence spectroscopy of dispersions of vesicles and (ii) potentiometric and potential step experiments across a free-standing bilayer membrane.
Results and Discussion
ARTICLE SECTIONS
We have previously reported the unexpected ability of the hydrophobic carborane-capped gold nanoparticles (2–3 nm) to disperse readily in aqueous media. (17) This is due to the storage of both electronic and ionic charge in the metallic core and in the ligand shell, respectively, as illustrated in Figure 1. Phase transfer experiments with cationic transfer agents have established the anionic character of the nanoparticles, and ion exchange with lithium followed by Li nuclear magnetic resonance (6Li NMR) spectroscopy has shown that alkali cations close to the metal surface compensate most of the excess electronic charge of the metal core. Removal of most charge by acid treatment renders the particles completely hydrophobic. It is useful to recall these findings when interpreting the results presented here.
Figure 1
Figure 1. Schematic representation of nanoparticles and charge storage. (a) Carborane-capped gold nanoparticles. (b) Charge storage in metallic core (electrons) and ligand shell (sodium ions) and formation of a water-dispersible polyanion by dissociation of sodium ions from the ligand shell. (17)
Before studying the ability of these nanoparticles to act as ion transporters across biological membranes, it is necessary to consider their own propensity as large anions to partition across the membrane and to establish a membrane potential. For this purpose, we used an established experimental approach to monitor the membrane potential of phospholipid vesicles by fluorescence spectroscopy using the potential indicator dye safranin O that partitions between the membrane and the outer aqueous phase depending on membrane potential. (20, 21) The fluorescence intensity significantly increases when the dye molecules reside inside the membrane. Vesicles of 100–200 nm diameter with a positive ζ-potential (Table S1) were prepared following the method reported by Stupp and co-workers (22) and characterized by dynamic light scattering (DLS) and cryo-transmission electron microscopy (cryo-TEM) (Figure S1). For calibration purposes, their membrane potential was controlled by carefully adjusting the concentrations of K+ ions inside and outside the vesicles in the presence of the K+-specific transporter valinomycin. The fluorescence intensity of safranin O was calibrated against the membrane potential values calculated from the Nernst equation (Figure S2). (20, 23) If, instead of valinomycin, the nanoparticles are added, a rapid polarization of the membrane in the same direction (inside negative) is also observed, but the final value does not depend on the potassium concentrations on both sides of the membrane but only on the amount of nanoparticles added.
This effect is most pronounced in the absence of any added electrolyte other than the particles themselves (Figure 2b,c). If electrolytes are present, the polarizing effect of the Au/carborane NPs differs somewhat for different cations (Figure S3). We attribute this polarization to the anionic nanoparticles’ ability to transfer across the membrane and, in the absence of cation transport, to determine the membrane potential as the only partitioning ion. They are self-transporting partitioning ions. To quantify this in terms of a Nernst equilibrium, it is necessary to control the concentrations of nanoparticles on both sides of the membrane, which is not possible with the vesicle system but can be achieved using a droplet interface bilayer (DIB) separating two independently accessible electrolyte solutions, as elegantly demonstrated by Bayley et al. (Figure S4a). (24-26) The results are presented in Figure 2d. Although these direct measurements of membrane potential in this system are experimentally challenging and hence somewhat noisy, the results are robust and fully commensurate with the predictions from the Nernst equation. Also, the average charge per particle can now be inferred as −6 in 1 mM sodium chloride and −3 in 100 mM sodium chloride. At this stage, there is no evidence that the particles are capable of transporting ions across the membrane other than themselves.
Figure 2
Figure 2. Membrane polarization by Au/carborane NPs. (a) Schematic representation of membrane polarization after addition of anionic Au/carborane NPs to the aqueous medium outside the vesicles. While the particles readily transfer across the membrane, counterions remain on the outside of the vesicle. (b) Fluorescence response to the addition of Au/carborane NPs in a range of different concentrations in the absence of electrolyte. Note that polyethylene glycol-coated gold nanoparticles (Au/PEG-OH NPs) have no effect. (c) Membrane potential estimated from the data presented in (b). (d) Plot derived from the Nernst equation for two different NaCl concentrations. The membrane potentials were directly measured using a DIB cell (Figure S4a). Note the dependence of the charge of the Au/carborane NPs on the NaCl concentration, −3 at 100 mM and −6 at 1 mM. This is likely to be the case also for other alkali ions that can enter the ligand shell.
A different scenario presents itself when the membrane is first polarized by the presence of a potassium gradient using the potassium-specific transporter valinomycin (less than 2 molecules per vesicle). Figure 3a,b show how the membrane potential is built up and reaches its saturation value. If then the gold nanoparticles are added (1 to 2 particles per vesicle), an initial fast but small decline in fluorescence intensity is always observed. We interpret this as an artifact perhaps due to quenching and/or reabsorption of light by the metallic particle.
Figure 3
Figure 3. Monitoring the fluorescence of safranin O to probe the polarization and depolarization of the vesicle membrane. (a) All three traces show the initial polarization of the membrane after addition of valinomycin (11 nM) in the presence of safranin O (180 nM) in the medium outside the vesicles. The concentration of KCl was 100 mM inside and 0.1 mM outside the vesicles, and that of NaCl was 1 mM inside and 100.9 mM outside, which gives a positive polarity outside. Addition of Au/PEG-OH (20 nM) particles (black trace) leads to a rapid small decrease in fluorescence intensity but none attributable to change in membrane potential. This indicates that no charge is transferred by these particles. When instead Au/carborane NPs (20 nM) are added (red trace), besides the familiar small change in signal, the fluorescence decreased exponentially over 600 s. This is attributed to influx of sodium and efflux of potassium ions mediated by Au/carborane NPs and valinomycin. (b) Same as the red trace in (a) but with different potassium ions gradients, i.e., different saturation potentials. Depolarization of the membrane to a final value by Au/carborane NPs occurs over a wide range of potentials. (c) Red trace shows the same experiment as in (a), but the NPs were added first followed by addition of valinomycin (300 s). After the initial small polarization caused by NPs themselves, the membrane is polarized further upon addition of valinomycin. Note that after further polarization to an onset overpotential depolarization occurs as in (a) and (b). (d) Overpotentials for the onset of depolarization (black) and final potentials after depolarization (red) as a function of saturation membrane potential given by the potassium ion gradient (Figure S5).
Then, the fluorescence intensity decreases, gradually approaching a constant final value that quite accurately corresponds to the membrane potential the particles alone would have caused. The effective canceling of the potential initially determined by the potassium gradient is explained by the influx of Na+ and the efflux of K+ ions both from high to low concentration, indicating that the gold nanoparticles added under these conditions do provide a mechanism for Na+ transport across the membrane as well as for K+, in addition to valinomycin. As there are now transporters for sodium and potassium present in the membrane, both ions can freely flow in and out until their concentrations inside and outside the vesicles are equal and they cause the membrane potential to drop to zero (really to the small value determined by the partitioning of the nanoparticles). For a discussion of transport rates see Supporting Information (Index 7). While the nanoparticles were not found to transport ions that polarize the membrane, this experiment shows unequivocally that they support ion transport to depolarize the membrane in the presence of a competing polarizing mechanism. For comparison, if instead, our standard Au/PEG–OH nanoparticles of the same size are added, only the initial fast drop in signal intensity is observed but no subsequent depolarization of the membrane. (27) An unexpected phenomenon is revealed by an experiment identical to that shown in (Figure 3a,b) except that the nanoparticles are now added before the addition of valinomycin rather than afterward. The result is shown in Figure 3c. Upon addition of the particles, as expected, a small membrane potential is generated (30–40 mV inside negative) due to the partitioning of the anionic particles. When then valinomycin is added, the membrane is further polarized, making the inside more negative due to the increased K+ selectivity of the membrane induced by valinomycin. This initially confirms that the nanoparticles do not transport ions under these conditions, until the membrane potential reaches a value of 20–30 mV more negative inside than the potential caused by the particles alone. At this point, the membrane suddenly begins to depolarize gradually to the original value determined by the nanoparticles. We suggest that this empirical overpotential for depolarization is needed to activate the repartitioning of nanoparticles if they have prepolarized the membrane by having been added to one side only. After this initial polarization, the anionic particles will reside predominantly on the inside of the vesicles and will first have to cross the membrane before they can support the influx of sodium ions. The observed overpotential is always between 20 and 30 mV negative of the equilibrium potential caused by the particles alone. We believe that this would disappear if we had an equal concentration of particles on both sides of the membrane, which in the present system is experimentally not possible. A further shortcoming of this experimental approach is that we can only measure membrane potentials with an outside positive/inside negative polarity as it was not possible to prepare the vesicles with the potential sensitive dye incorporated inside, which would have been necessary to measure membrane potentials of opposite polarity. Also, ionic currents across the membranes are inferred but are not measured directly. To overcome these limitations and to validate our findings independently by an alternative method, we used planar bilayer membranes separated by two compartments of a small 3D-printed electrochemical cell (Figure S4b). (28, 29) These are conceptually similar to the DIB that have been used to measure the membrane potential caused by the partitioning of the nanoparticles. The current responses to alternating potential steps of up to −80/+80 mV applied across the membrane were recorded under various conditions. The results are shown in Figure 4. While sodium and potassium are both transported readily with a small preference for potassium, significant differences are found when comparing sodium and magnesium (Figure 4c,d). The intercept of −40 mV in Figure 4d indicates a clear preference for sodium over magnesium. This selectivity has also been observed by electrospray ionization time-of-flight (ESI-TOF) mass spectrometry after ion exchange experiments (Figure S6).
Figure 4
Figure 4. Current–voltage responses in potential step experiments on free-standing phospholipid bilayer membranes. (a) Current traces in response to potential steps of −80/+80 mV. The electrochemical cells are color coded underneath. Note that the largest currents are obtained in the presence of steep gradients of potassium and sodium concentrations across the membrane. (b) I–V curves corresponding to (a). Each point represents the steady-state current of the potential step experiment. The graph has been corrected to eliminate a small offset current (3–4 pA) that is present even in the absence of NPs. The intercept of +8 mV shows that K+ is preferentially transported over Na+. (c,d) Same as (a) and (b) but using sodium and magnesium instead. The intercept at −40 mV shows that sodium is transported preferentially to magnesium. This selectivity also indicates that simple defect formation in the membrane can be excluded as a transport mechanism.
The information provided by both approaches is consistent. The vesicle experiments have established that the nanoparticles act as cation transporters when they depolarize the membrane. Importantly, all attempts failed to polarize the membrane with partitioning ions that use the nanoparticles as transporter. Only the nanoparticles themselves can polarize the membrane regardless of the presence and concentration differences of other ions in the system. The depolarization of a prepolarized membrane is not possible if sodium is replaced by magnesium (Figure 5a,b), confirming the very low affinity of the particles for magnesium established by the electrochemical study. Further polarization of a prepolarized membrane is also not possible (Figure 5c,d), further confirming that the particles only transport ions if the resulting flow depolarizes the membrane. In this sense, the particles behave differently from a transporter such as valinomycin, which can be used to polarize the membrane with a potassium gradient. The particles alone will not do this; instead they always establish a membrane potential that is due to their own partitioning as anions.
Figure 5
Figure 5. (a) Polarization with potassium gradient after addition of valinomycin. Addition of Au/carborane NPs does not lead to depolarization if magnesium is chosen as the partitioning ion. (b) Same as (a) but the Au/carborane NPs were added before addition of valinomycin at 300 s. Again no depolarization occurs. (c) Polarization with potassium gradient after addition of valinomycin and attempt to further polarize the membrane using Au/carborane NPs as a transporter and sodium as partitioning ion. (d) Same as (c) but the NPs were added before of addition of valinomycin. All electrolyte concentrations are given in the insets.
The inability to polarize the membrane by the transport of cations in the presence of a concentration gradient strongly suggests that the particles do not simply open channels through which ions can freely flow across the membrane. A shuttle mechanism is more likely by which the particles fill up with cations on the side of high concentration, flip across the membrane, and release them on the side of low concentration, probably becoming more negative upon cation release unless the empty vacancies are immediately filled up with other cations. Only if the cations are released on the negatively polarized side of the membrane (depolarization) can the membrane potential push back the negatively charged particle to the positive side, where it is replenished with cations and the process repeats. Our current understanding of this process is summarized in Figure 6. Release of cations on the positive side of the membrane (polarization) would stop the process as the particle would remain trapped on that side of the membrane. The vesicle experiments also revealed that membrane depolarization requires an overpotential which we attribute to having the particles only added to one side of the membrane. Indeed, the electrochemical experiments do not show this overpotential and further seem to suggest that the particles act as transporters much like valinomycin (Figure S7). This is because by the very nature of these experiments, under potentiostatic control, the membrane is always polarized in such a way that cations cross the membrane from the positive to the negative side. The unusual property of the particles not to support a polarizing flow of cations would thus not have been noticed by the electrochemical investigation alone.
Figure 6
Figure 6. Scheme of membrane depolarization by transport of sodium and potassium ions. (I) Particles are added to the sodium rich dispersion of vesicles and adsorb to the vesicle membrane (Figure S8). Note, the membrane has been polarized (outside positive) by the presence of a potassium ion concentration gradient and the potassium specific carrier valinomycin (not shown). (II) As the particles penetrate the membrane, sodium ions are released inside the vesicle (down their concentration gradient). (III) As long as particles reside within the membrane, they can shuttle sodium ions across by passive transport down their concentration gradient. In parallel with the mechanism provided by valinomycin, the particles could also contribute to the export of potassium. The process stops when the concentrations of sodium and potassium inside and outside the vesicles are equal. The remaining potential of the depolarized membrane is then due to the partitioning of the anionic nanoparticles.
Conclusion
ARTICLE SECTIONS
In conclusion, we have demonstrated by two complementary experimental approaches that cation transport across phospholipid membranes can be facilitated by ligand-capped gold nanoparticles, which by themselves are large partitioning anions that form a Nernst equilibrium and result in the buildup of a membrane potential. Electrochemical experiments have established little selectivity within the alkali ions tested but high selectivity of alkali over alkaline earth ions. A condition for the particles’ activity as transporters is that the membrane potential is kept away from the equilibrium potential determined by the particles. This is done by either providing a chemical potential difference and an ion selective pathway or by controlling the membrane potential directly with a potentiostat. In the absence of both, the particles do not act as transporters for any ions but themselves and cannot be used, for example, like valinomycin, to polarize a membrane with a suitable partitioning ion.
Our findings establish functionalized nanoparticles as a class of ion transporters with some interesting properties. The phenomena observed suggest a simple model of a nanoscale electrostatically driven shuttle. The presence of the metallic core should, in parallel, enable electronic conduction which would create interesting opportunities for the use of biological membranes. The design of nano- and microscale systems with coupled electronic and ionic transport between compartments separated by a membrane is the subject of ongoing research in our laboratories.
Methods
ARTICLE SECTIONS
Chemicals
Hydrogen tetrachloroaurate(III) hydrate (HAuCl4·3H2O) and sodium borohydride (NaBH4) were supplied by Aldrich. Both cationic liposome kit and asolectin from soybean were purchased from Sigma. HS-C11-PEG4-OH was supplied by ProChimia. The cationic exchange resin, strongly acidic PA with a total exchange capacity of 2.0 mequiv/mL, and a water content of 46–52%, loaded with the desired cation chloride was provided by Panreac. Mercaptocarborane, 1-SH-1,2-closo-C2B10H11, was synthesized according to the literature. (30, 31) All salts were purchased from Sigma. Synthetic grade methanol, ethanol, and Milli-Q-grade (MQ) water were used in all preparations.
Unilamellar Vesicles
A 10 mM stock solution of phospholipids was made by dilution of lyophilized powder from a liposome kit (cholesterol 9 μmol, l-α-phosphatidylcholine 63 μmol, stearylamine 18 μmol) in chloroform. (22, 23) One milliliter aliquots of the stock solution were rotary evaporated to dryness and for a further 2 h in order to remove all residues of organic solvent. MQ water or KCl, Na2SO4, K2SO4 buffer solutions were used to hydrate the phospholipids depending on the requirements of each experiment (agitate overnight). In order to make the suspension of phospholipids more homogeneous, it was heated to 60 °C followed by 6–9 freeze–thaw cycles using liquid nitrogen. Next, the homogeneous phospholipid solution was extruded 20 times through a mini-extruder (Avanti) with a 100 nm pore-size polycarbonate filter (Whatman) to form vesicles of about 100 nm diameters. Purification of such prepared vesicles and buffer exchange were carried out by using dialysis tubing MWCO 12000–14000 (Serva).
Preparation of Ligand-Capped 2–3 nm Gold Nanoclusters
Both Au/PEG-OH and Au/carborane gold nanoclusters were synthesized following a literature method. (17) All the reaction components were mixed in the following final concentrations: capping agents [HS-C11-PEG4-OH] or [mercaptocarborane] = 3 mM, [HAuCl4] = 3 mM, [NaBH4] = 9.5 mM. In the case of mercaptocarborane-capped gold nanoclusters solvent was rota evaporated followed by washing of excess capping agent molecules with diethyl ether. In the final step, dark-brown residue was dissolved in isopropyl alcohol and filtered to remove the remaining sodium borohydride and other insoluble contaminants. PEGylated gold nanoclusters were washed by using ultra-high-speed centrifuge at 163000 rcf for 1 h, and the pellet was redispersed in a 9:1 mixture of water and ethanol. In total, the purification process was repeated three times where final product was redispersed in MQ water only. All particles were additionally characterized by ultraviolet–visible spectroscopy (UV–vis), high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared spectroscopy (FTIR) (Figures S9 and S10).
Membrane Potential Changes Monitored by Fluorescence Spectroscopy
The suspension of vesicles with a final concentration of phospholipids of 1 mM was placed in a fluorimetric cuvette followed by addition of the potential probe dye safranin O (180 nM final concentration). Then the fluorescence intensity was allowed to equilibrate for 2 min. The kinetic mode was used to detect continuous fluorescence intensity changes at 589 nm with an excitation wavelength of 521 nm. In membrane depolarization experiments, concentrations varying from 11 to 15 nM valinomycin, and 20 nM Au/carborane NPs were used. The fluorescence intensity was monitored over 2000 s. Experiments including NaCl, KCl, and MgCl2 salts were performed at a pH range of 6.8–6.9. Experiment including sulfates (Figure 5c,d) was carried out in similar pH values 6.8–6.9 using 10 mM sodium phosphate buffer.
Membrane Formation in the Droplet Interface Bilayer Cell
The chamber of a 3D-printed polyacrylamide cell (Figure S4a) was filled with aqueous electrolyte (300 μL), and then a lipid-containing decane solution (150 μL) was added on the top, so that a lipid monolayer formed at the interface. A droplet of electrolyte (∼3 μL) was pipetted onto an agarose-coated Ag/AgCl electrode and maneuvered, using a micromanipulator, so that the droplet was in the lipid–decane solution, where a monolayer of lipids surrounded the droplet. It was then moved to be in contact with the interface monolayer, where a bilayer membrane formed between the two aqueous phases. The formation of the membranes was tracked by using electrochemical methods. The average value of capacitance of membranes created using this procedure was 16 ± 2 nF, and resistance was in the range of 108–109 Ω. In each experiment, the membrane was formed with equal electrolyte and Au/carborane NP concentration in both aqueous phases called “in” and “out” (Figure S4a). Thereafter, gradual addition (via micropipette) of Au/carborane NPs to underlying planar aqueous medium (out) built up the concentration gradient of NPs across the membrane.
Formation of the Supported Planar Bilayer Membranes
Two Ag/AgCl electrodes were each fixed into one of two compartments of a 3D-printed polyacrylamide cell, with an aperture of ∼270 μm diameter separating the two compartments (Figure S4b). Electrolyte solution (200 μL) was added into each compartment to cover the electrodes, but not enough for the aqueous phase to reach the aperture. Fifty microliters of phospholipid solution made of asolectin from soybean mixture dissolved in decane (25 mg/mL) was added on top of the aqueous phase and left for 20 min for monolayers to form at the interface between the aqueous and organic phases. The monolayers were brought into contact by raising the level of the aqueous phase, via alternating micropipette additions of electrolyte into each compartment, until the aperture was fully submerged. The formation of the membrane was monitored by cyclic voltammetry using a Metrohm μAutolab III potentiostat and confirmed via capacitance and resistance measurements. In a standard experiment, capacitance of the formed membrane was in the range of 80–170 pF, yielding average specific capacitance value of 0.248 ± 0.06 μF/cm2. Specific resistance of such formed membranes was in the range of 107–108 Ω·cm2. (32) In each experiment, either NPs or valinomycin were added to both sides cis and trans of phospholipid bilayer membrane, reaching their final concentration of 200 nM. All experiments were carried out at a pH range of 7.1–7.2 using 20 mM MOPS buffer (3-(N-morpholino)propanesulfonic acid).
ζ-Potential and DLS Measurements
The ζ-potential measurements were performed on the earlier purified nanoparticles and vesicle solutions. Three measurements, each including 10 runs, were used to estimate average ζ-potential value. Malvern Zetasizer Nano ZS Zen3600 was used for both ζ-potential and DLS measurements.
Infrared
Colloidal suspensions of gold nanoparticles were deposited on IR windows by using a drop-casting method. Aqueous solutions of Au/PEG-OH were drop-casted on the ZnSe and Au/carborane NPs suspended in ethanol on the CaF2 IR windows. Powder of pure mercaptocarborane ligand was characterized by using attenuated total reflection (ATR) mode.
HR-TEM
The Au NP samples were prepared by drop-casting 3 μL of Au NP colloidal dispersion onto a holey carbon film, 300 mesh copper TEM grid (Agar Scientific), which was then dried in air for an hour before insertion into the microscope. HR-TEM was performed on a JEOL JEM 2100FCs equipped with a spherical aberration corrector (CEOS GmbH), operating at an accelerating voltage of 200 kV.
Cryo-TEM
Holey carbon film, 300 mesh, or Quantifoil R2/2, 200 mesh copper TEM grids (Agar Scientific), was glow-discharged in a Quorum 150T S turbo-pumped glow-discharge system. The samples were prepared by mixing the lipid vesicle solution with 50 nM colloidal dispersion of Au NPs. Three microliters of the prepared solution was drop-casted onto a glow-discharged TEM grid placed inside an FEI Vitrobot Mk2 vitrification system that was set to 8 °C and relative humidity of 98%. The samples were blotted 2 × 2 s before being plunged into liquid ethane. Vitrified samples were transferred onto a Gatan 626 cryogenic sample holder and imaged on an FEI Tecnai Spirit G2 BioTWIN TEM operating at an accelerating voltage of 120 kV, using an Olympus-SIS MegaView III digital camera. Cryo-TEM imaging was performed in low-dose mode (electron beam current density of 6.3 e–/Å2 s, with the total electron dose per imaged area of <50 e–/Å2) at a defocus ranging from −0.5 to −1.5 μm. During cryo-TEM, the sample holder temperature was maintained below −179 °C.
The acquired electron microscopy images were processed using ImageJ 1.46r software (NIH).
Ion Exchange and MALDI-TOF MS
To replace the sodium counterbalancing ions by Li+, approximately 100 mg of prepared sodium-loaded Au/carborane NPs were dissolved in water. Then, the solution was passed repeatedly through a lithium ion exchange column and subsequently analyzed by 7Li NMR spectroscopy. (17) Moreover, we interchanged the initial Na+ cation with K+, Mg2+, and Ca2+, by passing a solution of water-soluble sodium reached Au/carborane nanoparticles through the cation-exchange resin previously loaded with the corresponding cation (K+, Mg2+, and Ca2+). ESI-TOF mass spectra of the ethanol solutions of the Au/carborane NPs after the ion exchange were measured in the positive-ion mode using a home-built mass spectrometer. (33) Results showed that Na+ can be interchanged only by other alkali metals such as Li+ or K+. With alkali-earth metals, such as Mg2+ and Ca2+, there is no cation exchange even if the aqueous solution of the Au/carborane is passed more than 7 times through the resin as represented in (Figure S6).
Supporting Information
ARTICLE SECTIONS
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.7b06600.
Table 1 and Figures S1–S10 as referred to in the text (PDF)
Terms & Conditions
Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.
Author Information
ARTICLE SECTIONS
- Marcin P. Grzelczak - Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, United Kingdom;http://orcid.org/0000-0002-3215-1044;
- Mathias Brust - Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, United Kingdom;http://orcid.org/0000-0001-6301-7123;
- Tatsuya Tsukuda - Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;http://orcid.org/0000-0002-0190-6379
- Clara Viñas - Institut de Ciencia de Materials de Barcelona, ICMAB-CSIC, Campus UAB, E-08193 Bellaterra, Spain;http://orcid.org/0000-0001-5000-0277
- Francesc Teixidor - Institut de Ciencia de Materials de Barcelona, ICMAB-CSIC, Campus UAB, E-08193 Bellaterra, Spain;http://orcid.org/0000-0002-3010-2417
Acknowledgment
ARTICLE SECTIONS
The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC-Advanced Grant Project 321172 PANDORA. We would like to thank T. Watanabe for carrying out the mass spectrometry experiments.
References
ARTICLE SECTIONS
This article references 33 other publications.
- 1Hamill, O. P.; Marty, A.; Neher, E.; Sakmann, B.; Sigworth, F. J. Improved Patch-Clamp Techniques for High-Resolution Current Recording from Cells and Cell-Free Membrane Patches Pfluegers Arch. 1981, 391, 85– 100 DOI: 10.1007/BF00656997[Crossref], [PubMed], [CAS], Google Scholar1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaL38%252FjslWrug%253D%253D&md5=c981295f57b3239ca3719093b059f44dImproved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patchesHamill O P; Marty A; Neher E; Sakmann B; Sigworth F JPflugers Archiv : European journal of physiology (1981), 391 (2), 85-100 ISSN:0031-6768.1. The extracellular patch clamp method, which first allowed the detection of single channel currents in biological membranes, has been further refined to enable higher current resolution, direct membrane patch potential control, and physical isolation of membrane patches. 2. A description of a convenient method for the fabrication of patch recording pipettes is given together with procedures followed to achieve giga-seals i.e. pipette-membrane seals with resistances of 10(9) - 10(11) omega. 3. The basic patch clamp recording circuit, and designs for improved frequency response are described along with the present limitations in recording the currents from single channels. 4. Procedures for preparation and recording from three representative cell types are given. Some properties of single acetylcholine-activated channels in muscle membrane are described to illustrate the improved current and time resolution achieved with giga-seals. 5. A description is given of the various ways that patches of membrane can be physically isolated from cells. This isolation enables the recording of single channel currents with well-defined solutions on both sides of the membrane. Two types of isolated cell-free patch configurations can be formed: an inside-out patch with its cytoplasmic membrane face exposed to the bath solution, and an outside-out patch with its extracellular membrane face exposed to the bath solution. 6. The application of the method for the recording of ionic currents and internal dialysis of small cells is considered. Single channel resolution can be achieved when recording from whole cells, if the cell diameter is small (less than 20 micrometer). 7. The wide range of cell types amenable to giga-seal formation is discussed.
- 2Neher, E.; Sakmann, B. Single-Channel Currents Recorded from Membrane of Denervated Frog Muscle Fibres Nature 1976, 260, 799– 802 DOI: 10.1038/260799a0[Crossref], [PubMed], [CAS], Google Scholar2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaE287nsVGhtA%253D%253D&md5=f88eb7e304314635339f9ede4f7a4827Single-channel currents recorded from membrane of denervated frog muscle fibresNeher E; Sakmann BNature (1976), 260 (5554), 799-802 ISSN:0028-0836.There is no expanded citation for this reference.
- 3Doyle, D. A.; Morais Cabral, J.; Pfuetzner, R. A.; Kuo, A.; Gulbis, J. M.; Cohen, S. L.; Chait, B. T.; MacKinnon, R. The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity Science 1998, 280, 69– 77 DOI: 10.1126/science.280.5360.69[Crossref], [PubMed], [CAS], Google Scholar3https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXitlWksrY%253D&md5=1656f2dd67f573c8a9bce42cd06bd5beThe structure of the potassium channel: molecular basis of K+ conduction and selectivityDoyle, Declan A.; Cabral, Joao Morais; Pfuetzner, Richard A.; Kuo, Anling; Gulbis, Jacqueline M.; Cohen, Steven L.; Chait, Brian T.; MacKinnon, RoderickScience (Washington, D. C.) (1998), 280 (5360), 69-77CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review with 34 refs. The K+ channel from Streptomyces lividans is an integral membrane protein with sequence similarity to all known K+ channels, particularly in the pore region. X-ray anal. with data to 3.2 Å reveals that 4 identical subunits create an inverted teepee, or cone, cradling the selectivity filter of the pore in its outer end. The narrow selectivity filter is only 12 Å long, whereas the remainder of the pore is wider and lined with hydrophobic amino acids. A large water-filled cavity and helix dipoles are positioned so as to overcome electrostatic destabilization of an ion in the pore at the center of the bilayer. The main-chain carbonyl O atoms from the K+ channel signature sequence line the selectivity filter, which is held open by structural constraints to coordinate K+ ions but not smaller Na+ ions. The selectivity filter contains 2 K+ ions ∼7.5 Å apart. This configuration promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between K+ ions and the selectivity filter. The architecture of the pore establishes the phys. principles underlying selective K+ conduction.
- 4Dutzler, R.; Campbell, E. B.; Cadene, M.; Chait, B. T.; MacKinnon, R. X-Ray Structure of a ClC Chloride Channel at 3.0 Å Reveals the Molecular Basis of Anion Selectivity Nature 2002, 415, 287– 294 DOI: 10.1038/415287a[Crossref], [PubMed], [CAS], Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XptlWksA%253D%253D&md5=2f966e52e8f9ab532d1e65d1661b9a15X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivityDutzler, Raimund; Campbell, Ernest B.; Cadene, Martine; Chait, Brian T.; MacKinnon, RoderlelcNature (London, United Kingdom) (2002), 415 (6869), 287-294CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)The ClC Cl- channels catalyze the selective flow of Cl- ions across cell membranes, thereby regulating elec. excitation in skeletal muscle and the flow of salt and water across epithelial barriers. Genetic defects in ClC Cl- channels underlie several familial muscle and kidney diseases. Here, the authors present the x-ray crystal structures of 2 prokaryotic ClC Cl- channels from Salmonella enterica serovar typhimurium and Escherichia coli at 3.0 and 3.5 Å, resp. Both structures revealed 2 identical pores, each pore being formed by a sep. subunit contained within a homodimeric membrane protein. Individual subunits were composed of 2 roughly repeated halves that spanned the membrane with opposite orientations. This antiparallel architecture defined a selectivity filter in which a Cl- ion was stabilized by electrostatic interactions with α-helix dipoles and by chem. coordination with N atoms and OH groups. These findings provide a structural basis for further understanding the function of ClC Cl- channels, and establish the phys. and chem. basis of their anion selectivity.
- 5Yeagle, P. L. Membrane Transport. In The Membranes of Cells, 3rd ed.; Yeagle, P. L., Ed.; Academic Press: Boston, MA, 2016; pp 335– 378.
- 6Stein, W. D.; Litman, T. Carrier-Mediated Transport: Facilitated Disfusion. In Channels, Carriers, and Pumps: An Introduction to Membrane Transport, 2nd ed.; Stein, W. D.; Litman, T., Eds.; Elsevier: London, 2015; pp 131– 178.
- 7Davies, M. Concept Underlie Models. In Functions of Biological Membranes; Chapman & Hall: London, 1973; pp 27– 54.
- 8Petty, H. R. Bioenergetics: Putting Membranes to Work. In Molecular Biology of Membranes: Structure and Function; Springer: New York, 1993; pp 123– 188.
- 9Ghadiri, M. R.; Granja, J. R.; Buehler, L. K. Artificial Transmembrane Ion Channels from Self-Assembling Peptide Nanotubes Nature 1994, 369, 301– 304 DOI: 10.1038/369301a0[Crossref], [PubMed], [CAS], Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXlsleit7k%253D&md5=f895d679b881bb5dada23e22afb4aa9cArtificial transmembrane ion channels from self-assembling peptide nanotubesGhadiri, M. Reza; Granja, Juan R.; Buehler, Lukas K.Nature (London, United Kingdom) (1994), 369 (6478), 301-4CODEN: NATUAS; ISSN:0028-0836.Naturally occurring membrane channels and pores are formed from a large family of diverse proteins, peptides and org. secondary metabolites whose vital biol. functions include control of ion flow, signal transduction, mol. transport and prodn. of cellular toxins. But despite the availability of a large amt. of biochem. information about these mols., the design and synthesis of artificial systems that can mimic the biol. function of natural compds. remains a formidable task. Here the authors present a simple strategy for the design of artificial membrane ion channels based on a self-assembled cylindrical β-sheet peptide architecture. The authors' systems-essentially stacks of peptide rings-display good channel-mediated ion-transport activity with rates exceeding 107 ions s-1, rivalling the performance of many naturally occurring counterparts. Such mol. assemblies should find use in the design of novel cytotoxic agents, membrane transport vehicles and drug-delivery systems.
- 10Fyles, T. M.; Loock, D.; Zhou, X. A Voltage-Gated Ion Channel Based on a Bis-Macrocyclic Bolaamphiphile J. Am. Chem. Soc. 1998, 120, 2997– 3003 DOI: 10.1021/ja972648q[ACS Full Text
], [CAS], Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXhslyqsr0%253D&md5=2871d4db4c17b3b0ef2bda7976342abfA Voltage-Gated Ion Channel Based on a Bis-Macrocyclic BolaamphiphileFyles, T. M.; Loock, D.; Zhou, X.Journal of the American Chemical Society (1998), 120 (13), 2997-3003CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The synthesis and characterization of dissym. bis-macrocyclic bolaamphiphile ion channel I is described. Bilayer-clamp expts. give rectified macroscopic current-voltage responses in which current is carried only at cis-neg. potentials. Voltage and orientation-dependent irregular single-channel activity is also obsd. Partial protonation of the carboxylate headgroups of the bolaamphiphile results in long-lived single channels with addnl. shorter-lived states of higher conductance. Single channels are also stabilized in the presence of barium cations. Vesicle expts. establish that transport activity is strongly cation- and concn.-dependent, suggesting the formation of aggregates. The voltage-gating process apparently involves the interaction of the applied potential with the mol. dipole of the bolaamphiphile which stabilizes an active aggregate. - 11Fyles, T. M. Synthetic Ion Channels in Bilayer Membranes Chem. Soc. Rev. 2007, 36, 335– 347 DOI: 10.1039/B603256G[Crossref], [PubMed], [CAS], Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtVKltbs%253D&md5=f18cf7b363a2ec3f7d8b61901027369fSynthetic ion channels in bilayer membranesFyles, Thomas M.Chemical Society Reviews (2007), 36 (2), 335-347CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Natural ion channels are large protein complexes that regulate key functions of cells. Supramol. chemists have been able to take hints from Nature to design and prep. completely synthetic ion channel systems that reproduce many of the fundamental functions of natural channels. This tutorial review introduces the field to non-specialists. It examines the design, synthesis, incorporation, and characterization of synthetic ion channels in bilayer membranes, and points to potential applications of synthetic ion channels.
- 12Langecker, M.; Arnaut, V.; Martin, T. G.; List, J.; Renner, S.; Mayer, M.; Dietz, H.; Simmel, F. C. Synthetic Lipid Membrane Channels Formed by Designed DNA Nanostructures Science 2012, 338, 932– 936 DOI: 10.1126/science.1225624[Crossref], [PubMed], [CAS], Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhs1GntL7O&md5=0988ffed136b4b1e7364327bde438c8fSynthetic Lipid Membrane Channels Formed by Designed DNA NanostructuresLangecker, Martin; Arnaut, Vera; Martin, Thomas G.; List, Jonathan; Renner, Stephan; Mayer, Michael; Dietz, Hendrik; Simmel, Friedrich C.Science (Washington, DC, United States) (2012), 338 (6109), 932-936CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)We created nanometer-scale transmembrane channels in lipid bilayers by means of self-assembled DNA-based nanostructures. Scaffolded DNA origami was used to create a stem that penetrated and spanned a lipid membrane, as well as a barrel-shaped cap that adhered to the membrane, in part via 26 cholesterol moieties. In single-channel electrophysiol. measurements, we found similarities to the response of natural ion channels, such as conductances on the order of 1 nanosiemens and channel gating. More pronounced gating was seen for mutations in which a single DNA strand of the stem protruded into the channel. Single-mol. translocation expts. show that the synthetic channels can be used to discriminate single DNA mols.
- 13Burns, J. R.; Seifert, A.; Fertig, N.; Howorka, S. A Biomimetic DNA-Based Channel for the Ligand-Controlled Transport of Charged Molecular Cargo across a Biological Membrane Nat. Nanotechnol. 2016, 11, 152– 156 DOI: 10.1038/nnano.2015.279[Crossref], [PubMed], [CAS], Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xns1ajtw%253D%253D&md5=532b1d0a5d1fdd47a02a2c5b3d697f28A biomimetic DNA-based channel for the ligand-controlled transport of charged molecular cargo across a biological membraneBurns, Jonathan R.; Seifert, Astrid; Fertig, Niels; Howorka, StefanNature Nanotechnology (2016), 11 (2), 152-156CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)Biol. ion channels are mol. gatekeepers that control transport across cell membranes. Recreating the functional principle of such systems and extending it beyond physiol. ionic cargo is both scientifically exciting and technol. relevant to sensing or drug release. However, fabricating synthetic channels with a predictable structure remains a significant challenge. Here, we use DNA as a building material to create an atomistically detd. mol. valve that can control when and which cargo is transported across a bilayer. The valve, which is made from seven concatenated DNA strands, can bind a specific ligand and, in response, undergo a nanomech. change to open up the membrane-spanning channel. It is also able to distinguish with high selectivity the transport of small org. mols. that differ by the presence of a pos. or neg. charged group. The DNA device could be used for controlled drug release and the building of synthetic cell-like or logic ionic networks.
- 14Howorka, S. Building Membrane Nanopores Nat. Nanotechnol. 2017, 12, 619– 630 DOI: 10.1038/nnano.2017.99[Crossref], [PubMed], [CAS], Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtFensrvJ&md5=5f621778669959fb6ef7bb201f435ad1Building membrane nanoporesHoworka, StefanNature Nanotechnology (2017), 12 (7), 619-630CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)A review. Membrane nanopores, hollow nanoscale barrels that puncture biol. or synthetic membranes, have become powerful tools in chem.- and biosensing and have achieved notable success in portable DNA sequencing. The pores can be self-assembled from a variety of materials, including proteins, peptides, synthetic org. compds. and, more recently, DNA. But which building material is best for which application, and what is the relation between pore structure and function. In this Review, the author critically compares the characteristics of the different building materials and explores the influence of the building material on pore structure, dynamics and function. The future challenges of developing nanopore technol. were also discussed, and it was considered what the next-generation of nanopore structures could be and where further practical applications might emerge.
- 15Maingi, V.; Burns, J. R.; Uusitalo, J. J.; Howorka, S.; Marrink, S. J.; Sansom, M. S. P. Stability and Dynamics of Membrane-Spanning DNA Nanopores Nat. Commun. 2017, 8, 14784– 14796 DOI: 10.1038/ncomms14784[Crossref], [PubMed], [CAS], Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXkslOhtrs%253D&md5=d45e6928601db5818cc7f7f9cb0a838eStability and dynamics of membrane-spanning DNA nanoporesMaingi, Vishal; Burns, Jonathan R.; Uusitalo, Jaakko J.; Howorka, Stefan; Marrink, Siewert J.; Sansom, Mark S. P.Nature Communications (2017), 8 (), 14784CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)Recently developed DNA-based analogs of membrane proteins have advanced synthetic biol. A fundamental question is how hydrophilic nanostructures reside in the hydrophobic environment of the membrane. Here, we use multiscale mol. dynamics (MD) simulations to explore the structure, stability and dynamics of an archetypical DNA nanotube inserted via a ring of membrane anchors into a phospholipid bilayer. Coarse-grained MD reveals that the lipids reorganize locally to interact closely with the membrane-spanning section of the DNA tube. Steered simulations along the bilayer normal establish the metastable nature of the inserted pore, yielding a force profile with barriers for membrane exit due to the membrane anchors. Atomistic, equil. simulations at two salt concns. confirm the close packing of lipid around of the stably inserted DNA pore and its cation selectivity, while revealing localized structural fluctuations. The wide-ranging and detailed insight informs the design of next-generation DNA pores for synthetic biol. or biomedicine.
- 16Baše, T.; Bastl, Z.; Plzák, Z.; Grygar, T.; Plešek, J.; Carr, M. J.; Malina, V.; Šubrt, J.; Boháček, J.; Večerníková, E.; Kříž, O. Carboranethiol-Modified Gold Surfaces. A Study and Comparison of Modified Cluster and Flat Surfaces Langmuir 2005, 21, 7776– 7785 DOI: 10.1021/la051122d[ACS Full Text], [CAS], Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmtlGrtr4%253D&md5=c44b0e4da8bfe2cfa54eccc03b17af3cCarboranethiol-Modified Gold Surfaces. A Study and Comparison of Modified Cluster and Flat SurfacesBase, Tomas; Bastl, Zdenek; Plzak, Zbynek; Grygar, Tomas; Plesek, Jaromir; Carr, Michael J.; Malina, Vaclav; Subrt, Jan; Bohacek, Jaroslav; Vecernikova, Eva; Kriz, OtomarLangmuir (2005), 21 (17), 7776-7785CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Four different carboranethiol derivs. were used to modify the surfaces of Au nanoparticles and flat Au films. The novel materials engendered from these modifications are extraordinarily stable species with surfaces that support self-assembled monolayers of 1-(HS)-1,2-C2B10H11, 1,2-(HS)2-1,2-C2B10H10, 1,12-(HS)2-1,12-C2B10H10, and 9,12-(HS)2-1,2-C2B10H10, resp. Surprisingly, characterization of these materials revealed that a no. of mols. of the carboranethiol derivs. are incorporated inside the nanoparticles. This structural feature was studied using a no. of techniques, including XPS, UV-visible, and IR spectroscopies. Thermal desorption expts. show that carborane mols. detach and leave the nanoparticle surface mostly as 1,2-C2B10H10 isotopic clusters, leaving S atoms bound to the Au surface. The surfaces of both the Au nanoparticles and the flat Au films are densely packed with carboranethiolate units. One carborane cluster mol. occupies an area of 6 to 7 surface Au atoms of the nanoparticle and 8 surface Au atoms of the flat film. XPS data showed that mols. of 1,12-(HS)2-1,12-C2B10H10 bind to the flat Au surface with only half of the thiol groups due to the steric demands of the icosahedral carborane skeleton. Electrochem. measurements indicate complete coverage of the modified Au surfaces with the carboranethiol mols.
- 17Cioran, A. M.; Musteti, A. D.; Teixidor, F.; Krpetić, Ž.; Prior, I. A.; He, Q.; Kiely, C. J.; Brust, M.; Viñas, C. Mercaptocarborane-Capped Gold Nanoparticles: Electron Pools and Ion Traps with Switchable Hydrophilicity J. Am. Chem. Soc. 2012, 134, 212– 221 DOI: 10.1021/ja203367h[ACS Full Text], [CAS], Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsFKktrnM&md5=810a0b8c776c11cd65c7f19b533c48d8Mercaptocarborane-Capped Gold Nanoparticles: Electron Pools and Ion Traps with Switchable HydrophilicityCioran, Ana M.; Musteti, Ana D.; Teixidor, Francesc; Krpetic, Zeljka; Prior, Ian A.; He, Qian; Kiely, Christopher J.; Brust, Mathias; Vinas, ClaraJournal of the American Chemical Society (2012), 134 (1), 212-221CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A simple single-phase method for the prepn. of ∼2 nm gold nanoparticles capped with mercaptocarborane ligands is introduced. The resultant monolayer protected clusters (MPCs) exhibit redox-dependent soly. and readily phase transfer between water and nonpolar solvents depending on the electronic and ionic charge stored in the metal core and in the ligand shell, resp. The particles and their properties were characterized by high angle annular dark field imaging in a scanning transmission electron microscope, elemental anal., centrifugal particle sizing, UV-visible and FTIR spectroscopy, and TGA and by 1H, 11B, and 7Li NMR spectroscopy. Cellular uptake of the MPCs by HeLa cells was studied by TEM, and the subsequent generation of reactive oxygen species inside the cells was evaluated by confocal fluorescence microscopy. These MPCs qual. showed significant toxicity and the ability to penetrate into most cell compartments with a strong tendency of finally residing inside membranes. Applications in catalysis, electrocatalysis, and biomedicine are envisaged.
- 18Schwartz, J. J.; Mendoza, A. M.; Wattanatorn, N.; Zhao, Y.; Nguyen, V. T.; Spokoyny, A. M.; Mirkin, C. A.; Baše, T.; Weiss, P. S. Surface Dipole Control of Liquid Crystal Alignment J. Am. Chem. Soc. 2016, 138, 5957– 5967 DOI: 10.1021/jacs.6b02026[ACS Full Text], [CAS], Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmtF2lsLc%253D&md5=2514f49df27761cb9e46d38a0f2af9f1Surface Dipole Control of Liquid Crystal AlignmentSchwartz, Jeffrey J.; Mendoza, Alexandra M.; Wattanatorn, Natcha; Zhao, Yuxi; Nguyen, Vinh T.; Spokoyny, Alexander M.; Mirkin, Chad A.; Base, Tomas; Weiss, Paul S.Journal of the American Chemical Society (2016), 138 (18), 5957-5967CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Detailed understanding and control of the intermol. forces that govern mol. assembly are necessary to engineer structure and function at the nanoscale. Liq. crystal (LC) assembly is exceptionally sensitive to surface properties, capable of transducing nanoscale intermol. interactions into a macroscopic optical readout. Self-assembled monolayers (SAMs) modify surface interactions and are known to influence LC alignment. Here, we exploit the different dipole magnitudes and orientations of carboranethiol and -dithiol positional isomers to deconvolve the influence of SAM-LC dipolar coupling from variations in mol. geometry, tilt, and order. Director orientations and anchoring energies are measured for LC cells employing various carboranethiol and -dithiol isomer alignment layers. The normal component of the mol. dipole in the SAM, toward or away from the underlying substrate, was found to det. the in-plane LC director orientation relative to the anisotropy axis of the surface. By using LC alignment as a probe of interaction strength, we elucidate the role of dipolar coupling of mol. monolayers to their environment in detg. mol. orientations. We apply this understanding to advance the engineering of mol. interactions at the nanoscale.
- 19Tonga, G. Y.; Saha, K.; Rotello, V. M. 25th Anniversary Article: Interfacing Nanoparticles and Biology: New Strategies for Biomedicine Adv. Mater. 2014, 26, 359– 370 DOI: 10.1002/adma.201303001[Crossref], [PubMed], [CAS], Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsF2ntb3P&md5=ae15be8a30c3adf99620a1bbfd05ac2225th Anniversary Article: Interfacing Nanoparticles and Biology: New Strategies for BiomedicineTonga, Gulen Yesilbag; Saha, Krishnendu; Rotello, Vincent M.Advanced Materials (Weinheim, Germany) (2014), 26 (3), 359-370CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The exterior surface of nanoparticles (NPs) dictates the behavior of these systems with the outside world. Understanding the interactions of the NP surface functionality with biosystems enables the design and fabrication of effective platforms for therapeutics, diagnostics, and imaging agents. In this review, we highlight the role of chem. in the engineering of nanomaterials, focusing on the fundamental role played by surface chem. in controlling the interaction of NPs with proteins and cells.
- 20Woolley, G.; Kapral, M.; Deber, C. Potential-Sensitive Membrane Association of a Fluorescent Dye FEBS Lett. 1987, 224, 337– 342 DOI: 10.1016/0014-5793(87)80480-5
- 21Si, W.; Li, Z. T.; Hou, J. L. Voltage-Driven Reversible Insertion into and Leaving from a Lipid Bilayer: Tuning Transmembrane Transport of Artificial Channels Angew. Chem., Int. Ed. 2014, 53, 4578– 4581 DOI: 10.1002/anie.201311249[Crossref], [CAS], Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXltFKlurc%253D&md5=1e80843d30560d7f0f5816e2815f06d0Voltage-Driven Reversible Insertion into and Leaving from a Lipid Bilayer: Tuning Transmembrane Transport of Artificial ChannelsSi, Wen; Li, Zhan-Ting; Hou, Jun-LiAngewandte Chemie, International Edition (2014), 53 (18), 4578-4581CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)Three new artificial transmembrane channel mols. have been designed and synthesized by attaching pos. charged Arg-incorporated tripeptide chains to pillar[5]arene. Fluorescent and patch-clamp expts. revealed that voltage can drive the mols. to insert into and leave from a lipid bilayer and thus switch on and off the transport of K+ ions. One of the mols. was found to display antimicrobial activity toward Bacillus subtilis with half maximal inhibitory concn. (IC50) of 10 μM which is comparable to that of natural channel-forming peptide alamethicin.
- 22Newcomb, C. J.; Sur, S.; Ortony, J. H.; Lee, O.-S.; Matson, J. B.; Boekhoven, J.; Yu, J. M.; Schatz, G. C.; Stupp, S. I. Cell Death versus Cell Survival Instructed by Supramolecular Cohesion of Nanostructures Nat. Commun. 2014, 5, 3321 DOI: 10.1038/ncomms4321[Crossref], [PubMed], [CAS], Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cvlsFOqtg%253D%253D&md5=3baf11f7a1278e14392fb71219011d05Cell death versus cell survival instructed by supramolecular cohesion of nanostructuresNewcomb Christina J; Sur Shantanu; Ortony Julia H; Matson John B; Boekhoven Job; Yu Jeong Min; Lee One-Sun; Schatz George C; Stupp Samuel INature communications (2014), 5 (), 3321 ISSN:.Many naturally occurring peptides containing cationic and hydrophobic domains have evolved to interact with mammalian cell membranes and have been incorporated into materials for non-viral gene delivery, cancer therapy or treatment of microbial infections. Their electrostatic attraction to the negatively charged cell surface and hydrophobic interactions with the membrane lipids enable intracellular delivery or cell lysis. Although the effects of hydrophobicity and cationic charge of soluble molecules on the cell membrane are well known, the interactions between materials with these molecular features and cells remain poorly understood. Here we report that varying the cohesive forces within nanofibres of supramolecular materials with nearly identical cationic and hydrophobic structure instruct cell death or cell survival. Weak intermolecular bonds promote cell death through disruption of lipid membranes, while materials reinforced by hydrogen bonds support cell viability. These findings provide new strategies to design biomaterials that interact with the cell membrane.
- 23Grzelczak, M. P.; Hill, A. P.; Belic, D.; Bradley, D. F.; Kunstmann-Olsen, C.; Brust, M. Design of Artificial Membrane Transporters from Gold Nanoparticles with Controllable Hydrophobicity Faraday Discuss. 2016, 191, 495– 510 DOI: 10.1039/C6FD00037A[Crossref], [PubMed], [CAS], Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmvFahsbg%253D&md5=950d91fdb51113f33a1870cbf07bfb74Design of artificial membrane transporters from gold nanoparticles with controllable hydrophobicityGrzelczak, Marcin P.; Hill, Alexander P.; Belic, Domagoj; Bradley, Dan F.; Kunstmann-Olsen, Casper; Brust, MathiasFaraday Discussions (2016), 191 (Nanoparticles with Morphological and Functional Anisotropy), 495-510CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Gold nanoparticles with variable hydrophobicity have been prepd. in three different size regimes following established methods. The control of hydrophobicity was achieved by complexation of the 18-crown-6-CH2-thiolate ligand shell with potassium ions. Potassium dependent phase transfer of these particles from dispersion in water to chloroform was demonstrated, and the equil. partitioning of the particles in water-chloroform liq./liq. systems was quantified by optical spectroscopy. The gradual complexation of the ligand shell with potassium ions was further monitored by zeta potential measurements. Potassium dependent insertion of nanoparticles into the phospholipid bilayer membrane of vesicles in aq. dispersion has been demonstrated by cryogenic transmission electron microscopy (cryo-TEM). Nanoparticle-dependent potassium ion transport across the vesicle membrane has been established by monitoring the membrane potential with fluorescence spectroscopy using a potential sensitive dye.
- 24Tsofina, L. M.; Liberman, E. A.; Babakov, A. V. Production of Bimolecular Protein-Lipid Membranes in Aqueous Solution Nature 1966, 212, 681– 683 DOI: 10.1038/212681a0
- 25Holden, M. A.; Needham, D.; Bayley, H. Functional Bionetworks from Nanoliter Water Droplets J. Am. Chem. Soc. 2007, 129, 8650– 8655 DOI: 10.1021/ja072292a[ACS Full Text], [CAS], Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXmsV2ls7c%253D&md5=6968a13bbc0e7ed88ec1f2dd2bd5b961Functional Bionetworks from Nanoliter Water DropletsHolden, Matthew A.; Needham, David; Bayley, HaganJournal of the American Chemical Society (2007), 129 (27), 8650-8655CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The authors form networks from aq. droplets by submerging them in an oil/lipid mixt. When the droplets are joined together, the lipid monolayers surrounding them combine at the interface to form a robust lipid bilayer. Various protein channels and pores can incorporate into the droplet-interface bilayer (DIB), and the application of a potential with electrodes embedded within the droplets allows ionic currents to be driven across the interface and measured. By joining droplets in linear or branched geometries, functional bionetworks can be created. Although the interfaces between neighboring droplets comprise only single lipid bilayers, the structures of the networks are long-lived and robust. Indeed, a single droplet can be "surgically" excised from a network and replaced with a new droplet without rupturing adjacent DIBs. Networks of droplets can be powered with internal "biobatteries" that use ion gradients or the light-driven proton pump bacteriorhodopsin. Besides their interest as coupled protocells, the droplets can be used as devices for ultrastable bilayer recording with greatly reduced electrolyte vol., which will permit their use in rapid screening applications.
- 26Bayley, H.; Cronin, B.; Heron, A.; Holden, M. A.; Hwang, W. L.; Syeda, R.; Thompson, J.; Wallace, M. Droplet Interface Bilayers Mol. BioSyst. 2008, 4, 1191– 1208 DOI: 10.1039/b808893d[Crossref], [PubMed], [CAS], Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhtlOhtb%252FM&md5=9bcd12423de5096c200ed48d2e868c86Droplet interface bilayersBayley, Hagan; Cronin, Brid; Heron, Andrew; Holden, Matthew A.; Hwang, William L.; Syeda, Ruhma; Thompson, James; Wallace, MarkMolecular BioSystems (2008), 4 (12), 1191-1208CODEN: MBOIBW; ISSN:1742-206X. (Royal Society of Chemistry)A review. Droplet interface bilayers (DIBs) provide a superior platform for the biophys. anal. of membrane proteins. The versatile DIBs can also form networks, with features that include built-in batteries and sensors.
- 27Gordillo, G. J.; Krpetić, Z.; Brust, M. Interactions of Gold Nanoparticles with a Phospholipid Monolayer Membrane on Mercury ACS Nano 2014, 8, 6074– 6080 DOI: 10.1021/nn501395e[ACS Full Text], [CAS], Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXptVWrurY%253D&md5=508a20f0ed7bf6b44663f5ed7095d1d3Interactions of Gold Nanoparticles with a Phospholipid Monolayer Membrane on MercuryGordillo, Gabriel J.; Krpetic, Zeljka; Brust, MathiasACS Nano (2014), 8 (6), 6074-6080CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)It is demonstrated that a compact monolayer of 1,2-dioleoyl-sn-glycero-3-phosphocholine adsorbed to a hanging mercury drop electrode can serve as a simple electrochem. model system to study biomembrane penetration by gold nanoparticles. The hydrogen redox-chem. characteristic of ligand-stabilized gold nanoparticles in molecularly close contact with a mercury electrode is used as an indicator of membrane penetration. Results for water-dispersible gold nanoparticles of two different sizes are reported, and comparisons are made with the cellular uptake of the same prepns. of nanoparticles by a common human fibroblast cell line. The exptl. system described here can be used to study physicochem. aspects of membrane penetration in the absence of complex biol. mechanisms, and it could also be a starting point for the development of a test bed for the toxicity of nanomaterials.
- 28Montal, M.; Mueller, P. Formation of Bimolecular Membranes from Lipid Monolayers and a Study of Their Electrical Properties Proc. Natl. Acad. Sci. U. S. A. 1972, 69, 3561– 3566 DOI: 10.1073/pnas.69.12.3561[Crossref], [PubMed], [CAS], Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE3sXmvVGhtA%253D%253D&md5=1593b730b0ddae8a6960806395e644a8Formation of bimolecular membranes from lipid monolayers and a study of their electrical propertiesMontal, M.; Mueller, P.Proceedings of the National Academy of Sciences of the United States of America (1972), 69 (12), 3561-6CODEN: PNASA6; ISSN:0027-8424.Bimol. membranes are formed from 2 lipid monolayers at an air-water interface by the apposition of their hydrocarbon chains when an aperture in a Teflon partition sepg. 2 aq. phases is lowered through the interface. Formation of the membrane is monitored by an increase of the elec. capacity, as measured with a voltage clamp. Elec. resistance of the unmodified membrane is analogous to that of conventional planar bilayers (black lipid membranes) prepd. in the presence of a hydrocarbon solvent, i.e. 106-108 ohm cm2; the resistance can be lowered to values of 103 ohm cm2 by gramicidin, an antibiotic that modifies the conductance only when the membranes are of bimol. thickness. In contrast to the resistance, there is a significant difference between the capacity of bilayers made from monolayers and that of hydrocarbon-contg. bilayers made by phase transition; the av. values are 0.9 and 0.45 μF cm-2, resp. The value of 0.9 μF cm-2 approximates that of biological membranes. Assuming a dielectric constant of 2.1 for the hydrocarbon region, the dielectric thickness, as calculated from a capacity of 0.9 μF cm-2, is 22 Å. This value is 6-10 Å smaller than the actual thickness of the hydrocarbon region of bilayers and cell membranes, as detd. by x-ray diffraction. The difference may be due to a limited penetration of water into the hydrocarbon region near the ester groups that would lower the electrical resistance of this region and reduce the dielectric thickness. Asymmetric membranes have been formed by adjoining 2 lipid monolayers of different chemical compn.
- 29Montal, M. [50] Formation of Bimolecular Membranes from Lipid Monolayers Methods Enzymol. 1974, 32, 545– 554 DOI: 10.1016/0076-6879(74)32053-8
- 30Smith, H. D.; Obenland, C. O.; Papetti, S. A New Series of Organoboranes. IX. The Preparation and Some Reactions of Sulfur-Carborane Derivatives Inorg. Chem. 1966, 5, 1013– 1015 DOI: 10.1021/ic50040a014[ACS Full Text], [CAS], Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF28XktFansr4%253D&md5=2be7cb726e9a6b277864b75e4410864dA new series of organoboranes. IX. The preparation and some reactions of sulfur-carborane derivativesSmith, H. D., Jr.; Obenland, C. O.; Papetti, S.Inorganic Chemistry (1966), 5 (6), 1013-15CODEN: INOCAJ; ISSN:0020-1669.cf. CA 63, 16378h; 64, 17627d. The first examples of S derivs. of o- and n-carborane are reported and the preparative reactions have been extended to include various B-bromocarboranes. Some chem. of these derivs. is described including the prepn. of an inner complex of Ni.
- 31Viñas, C.; Benakki, R.; Teixidor, F.; Casabo, J. Dimethoxyethane as a Solvent for the Synthesis of C-Monosubstituted O-Carborane Derivatives Inorg. Chem. 1995, 34, 3844– 3845 DOI: 10.1021/ic00118a041
- 32Puchkov, M. N.; Vassarais, R. A.; Korepanova, E. A.; Osipov, A. N. Cytochrome c Produces Pores in Cardiolipin-Containing Planar Bilayer Lipid Membranes in the Presence of Hydrogen Peroxide Biochim. Biophys. Acta, Biomembr. 2013, 1828, 208– 212 DOI: 10.1016/j.bbamem.2012.10.002[Crossref], [PubMed], [CAS], Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVKltw%253D%253D&md5=7ca9becad50db25d1efe07ac5b24c7ddCytochrome c produces pores in cardiolipin-containing planar bilayer lipid membranes in the presence of hydrogen peroxidePuchkov, M. N.; Vassarais, R. A.; Korepanova, E. A.; Osipov, A. N.Biochimica et Biophysica Acta, Biomembranes (2013), 1828 (2), 208-212CODEN: BBBMBS; ISSN:0005-2736. (Elsevier B.V.)Interaction of cytochrome c with cardiolipin in the presence of hydrogen peroxide induces peroxidase activity in cytochrome c and the ability to oxidize membrane lipids. These cytochrome c properties play a substantial role in the cytochrome c-mediated apoptotic reactions. In the present study the elec. properties (specific capacitance and integral conductance) of the cardiolipin-contg. asolectin planar bilayer lipid membranes (pBLM) in the presence of cytochrome c and hydrogen peroxide were studied. Cytochrome c interaction with cardiolipin-contg. pBLM in the presence of hydrogen peroxide resulted in the dramatic increase of the conductance, pore prodn., their growth up to 3.5 nm diam. and subsequent membrane destruction. In the absence of hydrogen peroxide cytochrome c demonstrated almost no effect on the membrane capacitance and conductance. The data obtained prove the pivotal role of cytochrome c and membrane lipids in the permeabilization of pBLM. Correlation of apoptotic reactions and cytochrome c-mediated membrane permeability is discussed.
- 33Negishi, Y.; Nobusada, K.; Tsukuda, T. Glutathione-Protected Gold Clusters Revisited: Bridging the Gap between Gold(I)–Thiolate Complexes and Thiolate-Protected Gold Nanocrystals J. Am. Chem. Soc. 2005, 127, 5261– 5270 DOI: 10.1021/ja042218h[ACS Full Text], [CAS], Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXisVGhtr8%253D&md5=a8fcd56538ee94fd3b86a580e2abd683Glutathione-Protected Gold Clusters Revisited: Bridging the Gap between Gold(I)-Thiolate Complexes and Thiolate-Protected Gold NanocrystalsNegishi, Yuichi; Nobusada, Katsuyuki; Tsukuda, TatsuyaJournal of the American Chemical Society (2005), 127 (14), 5261-5270CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Small gold clusters (∼1 nm) protected by mols. of a tripeptide, glutathione (GSH), were prepd. by reductive decompn. of Au(I)-SG polymers at a low temp. and sepd. into a no. of fractions by polyacrylamide gel electrophoresis (PAGE). Chem. compns. of the fractionated clusters detd. previously by electrospray ionization (ESI) mass spectrometry (Negishi, Y. et al. J. Am. Chem. Soc. 2004, 126, 6518) were reassessed by taking advantage of freshly prepd. samples, higher mass resoln., and more accurate mass calibration; the nine smallest components are reassigned to Au10(SG)10, Au15(SG)13, Au18(SG)14, Au22(SG)16, Au22(SG)17, Au25(SG)18, Au29(SG)20, Au33(SG)22, and Au39(SG)24. These assignments were further confirmed by measuring the mass spectra of the isolated Au:S(h-G) clusters, where h-GSH is a homoglutathione. It is proposed that a series of the isolated Au:SG clusters corresponds to kinetically trapped intermediates of the growing Au cores. The relative abundance of the isolated clusters was correlated well with the thermodn. stabilities against unimol. decompn. The electronic structures of the isolated Au:SG clusters were probed by XPS and optical spectroscopy. The Au(4f) XPS spectra illustrate substantial electron donation from the gold cores to the GS ligands in the Au:SG clusters. The optical absorption and photoluminescence spectra indicate that the electronic structures of the Au:SG clusters are well quantized; embryos of the sp band of the bulk gold evolve remarkably depending on the no. of the gold atoms and GS ligands. The comparison of these spectral data with those of sodium Au(I) thiomalate and 1.8 nm Au:SG nanocrystals (NCs) reveals that the subnanometer-sized Au clusters thiolated constitute a distinct class of binary system which lies between the Au(I)-thiolate complexes and thiolate-protected Au NCs.
Cited By
This article is cited by 41 publications.
- Miftah Faried, Keishi Suga, Yukihiro Okamoto, Kamyar Shameli, Mikio Miyake, Hiroshi Umakoshi. Membrane Surface-Enhanced Raman Spectroscopy for Cholesterol-Modified Lipid Systems: Effect of Gold Nanoparticle Size. ACS Omega 2019, 4 (9) , 13687-13695. https://doi.org/10.1021/acsomega.9b01073
- Alexander M. Spokoyny, , Ching-Wen Chiu, , Beth D. Bosley, , David M. Schubert. “Mr. Boron”, an Inorganic Chemistry Icon, Turns 90. Inorganic Chemistry 2019, 58 (9) , 5369-5374. https://doi.org/10.1021/acs.inorgchem.9b00913
- Hairong Lyu, Jie Zhang, Jingting Yang, Yangjian Quan, Zuowei Xie. Catalytic Regioselective Cage B(8)–H Arylation of o-Carboranes via “Cage-Walking” Strategy. Journal of the American Chemical Society 2019, 141 (10) , 4219-4224. https://doi.org/10.1021/jacs.9b00302
- Furong Lin, Jing-Lu Yu, Yunjun Shen, Shuo-Qing Zhang, Bernhard Spingler, Jiyong Liu, Xin Hong, Simon Duttwyler. Palladium-Catalyzed Selective Five-Fold Cascade Arylation of the 12-Vertex Monocarborane Anion by B–H Activation. Journal of the American Chemical Society 2018, 140 (42) , 13798-13807. https://doi.org/10.1021/jacs.8b07872
- Rachel Kozlowski, Ashwin Ragupathi, R. Brian Dyer. Characterizing the Surface Coverage of Protein–Gold Nanoparticle Bioconjugates. Bioconjugate Chemistry 2018, 29 (8) , 2691-2700. https://doi.org/10.1021/acs.bioconjchem.8b00366
- Ilgın Nar, Armağan Atsay, Ahmet Altındal, and Esin Hamuryudan . o-Carborane, Ferrocene, and Phthalocyanine Triad for High-Mobility Organic Field-Effect Transistors. Inorganic Chemistry 2018, 57 (4) , 2199-2208. https://doi.org/10.1021/acs.inorgchem.7b03097
- Francesc Teixidor, Rosario Núñez, Clara Viñas. Towards the Application of Purely Inorganic Icosahedral Boron Clusters in Emerging Nanomedicine. Molecules 2023, 28 (11) , 4449. https://doi.org/10.3390/molecules28114449
- Annette G. Beck-Sickinger, Daniel P. Becker, Oksana Chepurna, Bhaskar Das, Sebastian Flieger, Evamarie Hey-Hawkins, Narayan Hosmane, Satish S. Jalisatgi, Hiroyuki Nakamura, Rameshwar Patil, Maria da Graça H. Vicente, Clara Viñas. New Boron Delivery Agents. Cancer Biotherapy and Radiopharmaceuticals 2023, 38 (3) , 160-172. https://doi.org/10.1089/cbr.2022.0060
- Anatoly Soloviev, Irina Ivanova, Vadym Sydorenko, Khrystyna Sukhanova, Mariia Melnyk, Dariia Dryn, Alexander Zholos. Calcium‐dependent modulation of BK Ca channel activity induced by plasmonic gold nanoparticles in pulmonary artery smooth muscle cells and hippocampal neurons. Acta Physiologica 2023, 237 (3) https://doi.org/10.1111/apha.13922
- Meng Chen, Jingkai Xu, Deshi Zhao, Fangxiang Sun, Songlin Tian, Deshuang Tu, Changsheng Lu, Hong Yan. Site‐Selective Functionalization of Carboranes at the Electron‐Rich Boron Vertex: Photocatalytic B−C Coupling via a Carboranyl Cage Radical. Angewandte Chemie 2022, 134 (37) https://doi.org/10.1002/ange.202205672
- Meng Chen, Jingkai Xu, Deshi Zhao, Fangxiang Sun, Songlin Tian, Deshuang Tu, Changsheng Lu, Hong Yan. Site‐Selective Functionalization of Carboranes at the Electron‐Rich Boron Vertex: Photocatalytic B−C Coupling via a Carboranyl Cage Radical. Angewandte Chemie International Edition 2022, 61 (37) https://doi.org/10.1002/anie.202205672
- Fangxiang Sun, Shuaimin Tan, Hou‐Ji Cao, Jingkai Xu, Vladimir I. Bregadze, Deshuang Tu, Changsheng Lu, Hong Yan. Palladium‐Catalyzed Hydroboration of Alkynes with Carboranes: Facile Construction of a Library of Boron Cluster‐Based AIE‐Active Luminogens. Angewandte Chemie International Edition 2022, 61 (33) https://doi.org/10.1002/anie.202207125
- Fangxiang Sun, Shuaimin Tan, Hou‐Ji Cao, Jingkai Xu, Vladimir I. Bregadze, Deshuang Tu, Changsheng Lu, Hong Yan. Palladium‐Catalyzed Hydroboration of Alkynes with Carboranes: Facile Construction of a Library of Boron Cluster‐Based AIE‐Active Luminogens. Angewandte Chemie 2022, 134 (33) https://doi.org/10.1002/ange.202207125
- Shuting Li, Manting Li, Limin Chen, Jianying Yang, Zhao Wang, Fan Yang, Linhong He, Xinchun Li. Engineering highly efficient Li+ responsive nanochannels via host–guest interaction and photochemistry regulation. Journal of Colloid and Interface Science 2022, 615 , 674-684. https://doi.org/10.1016/j.jcis.2022.02.008
- Lukáš Fojt, Bohumír Grüner, Josef Holub, Luděk Havran, Miroslav Fojta. Electrochemistry of icosahedral metal full and half sandwich metallacarboranes in phosphate buffers. Journal of Electroanalytical Chemistry 2022, 910 , 116165. https://doi.org/10.1016/j.jelechem.2022.116165
- Lukáš Fojt, Bohumír Grüner, Jan Nekvinda, Ece Zeynep Tűzűn, Luděk Havran, Miroslav Fojta. Electrochemistry of Cobalta Bis(dicarbollide) Ions Substituted at Carbon Atoms with Hydrophilic Alkylhydroxy and Carboxy Groups. Molecules 2022, 27 (6) , 1761. https://doi.org/10.3390/molecules27061761
- Fangzuo Li, Qianqian Xu, Wenjing Xia, Xiang Zhang, Weidong Zhao, Lili Zhou, Haijian Zhong, Weijie Peng, Zhiguo Liu, Tianxi Sun. In situ small-angle X-ray scattering investigation of X-ray-induced gold nanoparticle synthesis without stabilizer. Journal of Applied Crystallography 2021, 54 (6) , 1711-1718. https://doi.org/10.1107/S1600576721010207
- Sina Hassanjani Saravi, Athanassios Z. Panagiotopoulos. Activity coefficients of aqueous electrolytes from implicit-water molecular dynamics simulations. The Journal of Chemical Physics 2021, 155 (18) , 184501. https://doi.org/10.1063/5.0064963
- Chiara Bellomo, Davide Zanetti, Francesca Cardano, Sohini Sinha, Mahdi Chaari, Andrea Fin, Andrea Maranzana, Rosario Núñez, Marco Blangetti, Cristina Prandi. Red light-emitting Carborane-BODIPY dyes: Synthesis and properties of visible-light tuned fluorophores with enhanced boron content. Dyes and Pigments 2021, 194 , 109644. https://doi.org/10.1016/j.dyepig.2021.109644
- Nicola William, Faith Bamidoro, Paul A. Beales, Rik Drummond-Brydson, Nicole Hondow, Sarah Key, Alexander Kulak, Aidan Charles Walsh, Sophia Winter, Laurence Andrew Nelson. Tuning stable noble metal nanoparticles dispersions to moderate their interaction with model membranes. Journal of Colloid and Interface Science 2021, 594 , 101-112. https://doi.org/10.1016/j.jcis.2021.03.009
- Marta Gozzi, Benedikt Schwarze, Evamarie Hey‐Hawkins. Preparing (Metalla)carboranes for Nanomedicine. ChemMedChem 2021, 16 (10) , 1533-1565. https://doi.org/10.1002/cmdc.202000983
- Xin‐Yu Wen, Ke Cao, Ji Wu, Cai‐Yan Zhang, Xia Li, Linhai Jiang, Junxiao Yang. Free Radical Polymerization of o ‐Carborane Functionalized Styrene: Effect of Substitution Position at Carbon and Boron. ChemistrySelect 2021, 6 (18) , 4491-4494. https://doi.org/10.1002/slct.202100932
- Muhammad Yaseen, Muhammad Humayun, Abbas Khan, Muhammad Usman, Habib Ullah, Asif Ali Tahir, Habib Ullah. Preparation, Functionalization, Modification, and Applications of Nanostructured Gold: A Critical Review. Energies 2021, 14 (5) , 1278. https://doi.org/10.3390/en14051278
- Casper Kunstmann-Olsen, Domagoj Belić, Dan F. Bradley, Stephen P. Danks, Yuri A. Diaz Fernandez, Marcin P. Grzelczak, Alexander P. Hill, Xiaohang Qiao, Rasmita Raval, Ioritz Sorzabal-Bellido, Mathias Brust. Ion shuttling between emulsion droplets by crown ether modified gold nanoparticles. Nanoscale Advances 2021, 401 https://doi.org/10.1039/D1NA00009H
- Jia-Bo Le, Qi-Yuan Fan, Jie-Qiong Li, Jun Cheng. Molecular origin of negative component of Helmholtz capacitance at electrified Pt(111)/water interface. Science Advances 2020, 6 (41) , eabb1219. https://doi.org/10.1126/sciadv.abb1219
- Minh Kim Nguyen, Ju-Young Moon, Young-Chul Lee. Microalgal ecotoxicity of nanoparticles: An updated review. Ecotoxicology and Environmental Safety 2020, 201 , 110781. https://doi.org/10.1016/j.ecoenv.2020.110781
- Frédéric Dumur, Eddy Dumas, Cédric R. Mayer. Functionalization of Gold Nanoparticles by Inorganic Entities. Nanomaterials 2020, 10 (3) , 548. https://doi.org/10.3390/nano10030548
- Damian Kaniowski, Katarzyna Ebenryter-Olbinska, Katarzyna Kulik, Slawomir Janczak, Anna Maciaszek, Katarzyna Bednarska-Szczepaniak, Barbara Nawrot, Zbigniew Lesnikowski. Boron clusters as a platform for new materials: composites of nucleic acids and oligofunctionalized carboranes (C 2 B 10 H 12 ) and their assembly into functional nanoparticles. Nanoscale 2020, 12 (1) , 103-114. https://doi.org/10.1039/C9NR06550D
- Valentina A. Ol'shevskaya, Andrey A. Tyutyunov, Lily F. Ibragimova, Elena G. Kononova, Evgeny G. Rys. Facile synthetic route to fluoroalkylated carboranes by copper-catalyzed reaction of fluoroalkane sulfonyl bromides with allyl carboranes. Polyhedron 2019, 171 , 508-514. https://doi.org/10.1016/j.poly.2019.08.004
- Arpita Saha, Abhishek Saini, Clara Vinas, Francesc Teixidor. The Next Stage in Colloidal Synthesis of Aqueous CdSe Quantum Dots: High Throughput and Intense Emissive Properties. ChemNanoMat 2019, 5 (7) , 940-947. https://doi.org/10.1002/cnma.201900247
- Takuto Aoki, Yuta Nakahama, Tadao Ikeda, Masako Shindo, Masanobu Uchiyama, Ken-ichi Shudo. Electronic states of 3D aromatic molecules on Au(111) surfaces: adsorption of carboranethiol. Journal of Materials Science 2019, 54 (14) , 10249-10260. https://doi.org/10.1007/s10853-019-03598-2
- Feiran Chen, Zhenggao Xiao, Le Yue, Jing Wang, Yan Feng, Xiaoshan Zhu, Zhenyu Wang, Baoshan Xing. Algae response to engineered nanoparticles: current understanding, mechanisms and implications. Environmental Science: Nano 2019, 6 (4) , 1026-1042. https://doi.org/10.1039/C8EN01368C
- Yunjun Shen, Kang Zhang, Xuewei Liang, Rakesh Dontha, Simon Duttwyler. Highly selective palladium-catalyzed one-pot, five-fold B–H/C–H cross coupling of monocarboranes with alkenes. Chemical Science 2019, 10 (15) , 4177-4184. https://doi.org/10.1039/C9SC00078J
- Marco S. Messina, Christian T. Graefe, Paul Chong, Omar M. Ebrahim, Ramya S. Pathuri, Nicholas A. Bernier, Harrison A. Mills, Arnold L. Rheingold, Renee R. Frontiera, Heather D. Maynard, Alexander M. Spokoyny. Carborane RAFT agents as tunable and functional molecular probes for polymer materials. Polymer Chemistry 2019, 10 (13) , 1660-1667. https://doi.org/10.1039/C9PY00199A
- Xing Wei, Meng‐Jiao Zhu, Zhe Cheng, Mengjeu Lee, Hong Yan, Changsheng Lu, Jing‐Juan Xu. Aggregation‐Induced Electrochemiluminescence of Carboranyl Carbazoles in Aqueous Media. Angewandte Chemie 2019, 131 (10) , 3194-3198. https://doi.org/10.1002/ange.201900283
- Xing Wei, Meng‐Jiao Zhu, Zhe Cheng, Mengjeu Lee, Hong Yan, Changsheng Lu, Jing‐Juan Xu. Aggregation‐Induced Electrochemiluminescence of Carboranyl Carbazoles in Aqueous Media. Angewandte Chemie International Edition 2019, 58 (10) , 3162-3166. https://doi.org/10.1002/anie.201900283
- Tatyana I. Rokitskaya, Ljudmila S. Khailova, Anton V. Makarenkov, Alexei V. Shunaev, Victor V. Tatarskiy, Alexander A. Shtil, Valentina A. Ol'shevskaya, Yuri N. Antonenko. Carborane derivatives of 1,2,3-triazole depolarize mitochondria by transferring protons through the lipid part of membranes. Biochimica et Biophysica Acta (BBA) - Biomembranes 2019, 1861 (3) , 573-583. https://doi.org/10.1016/j.bbamem.2018.12.009
- Clara Viñas, Rosario Núñez, Isabel Romero, Francesc Teixidor. Highlighting the Binding Behavior of Icosahedral Boron Clusters Incorporated into Polymers: Synthons, Polymers Preparation, and Relevant Properties. 2019, 41-60. https://doi.org/10.1002/9783527819140.ch2_2
- K.P. Divya, A. Anancia Grace, V. Dharuman. Rapid and sensitive electrochemical label free ion channel, membrane protein and DNA sensing on surface supported liposome-gold nanoparticle platform. Journal of Electroanalytical Chemistry 2019, 834 , 56-63. https://doi.org/10.1016/j.jelechem.2018.12.038
- Anahita Izadyar. Stripping Voltammetry at the Interface between two Immiscible Electrolyte Solutions: A Review Paper. Electroanalysis 2018, 30 (10) , 2210-2221. https://doi.org/10.1002/elan.201800279
- Mohammed Shariq, Bernd Friedrich, Bojan Budic, Nejc Hodnik, Francisco Ruiz-Zepeda, Peter Majerič, Rebeka Rudolf. Successful Synthesis of Gold Nanoparticles through Ultrasonic Spray Pyrolysis from a Gold(III) Nitrate Precursor and Their Interaction with a High Electron Beam. ChemistryOpen 2018, 7 (7) , 533-542. https://doi.org/10.1002/open.201800101
Abstract
Figure 1
Figure 1. Schematic representation of nanoparticles and charge storage. (a) Carborane-capped gold nanoparticles. (b) Charge storage in metallic core (electrons) and ligand shell (sodium ions) and formation of a water-dispersible polyanion by dissociation of sodium ions from the ligand shell. (17)
Figure 2
Figure 2. Membrane polarization by Au/carborane NPs. (a) Schematic representation of membrane polarization after addition of anionic Au/carborane NPs to the aqueous medium outside the vesicles. While the particles readily transfer across the membrane, counterions remain on the outside of the vesicle. (b) Fluorescence response to the addition of Au/carborane NPs in a range of different concentrations in the absence of electrolyte. Note that polyethylene glycol-coated gold nanoparticles (Au/PEG-OH NPs) have no effect. (c) Membrane potential estimated from the data presented in (b). (d) Plot derived from the Nernst equation for two different NaCl concentrations. The membrane potentials were directly measured using a DIB cell (Figure S4a). Note the dependence of the charge of the Au/carborane NPs on the NaCl concentration, −3 at 100 mM and −6 at 1 mM. This is likely to be the case also for other alkali ions that can enter the ligand shell.
Figure 3
Figure 3. Monitoring the fluorescence of safranin O to probe the polarization and depolarization of the vesicle membrane. (a) All three traces show the initial polarization of the membrane after addition of valinomycin (11 nM) in the presence of safranin O (180 nM) in the medium outside the vesicles. The concentration of KCl was 100 mM inside and 0.1 mM outside the vesicles, and that of NaCl was 1 mM inside and 100.9 mM outside, which gives a positive polarity outside. Addition of Au/PEG-OH (20 nM) particles (black trace) leads to a rapid small decrease in fluorescence intensity but none attributable to change in membrane potential. This indicates that no charge is transferred by these particles. When instead Au/carborane NPs (20 nM) are added (red trace), besides the familiar small change in signal, the fluorescence decreased exponentially over 600 s. This is attributed to influx of sodium and efflux of potassium ions mediated by Au/carborane NPs and valinomycin. (b) Same as the red trace in (a) but with different potassium ions gradients, i.e., different saturation potentials. Depolarization of the membrane to a final value by Au/carborane NPs occurs over a wide range of potentials. (c) Red trace shows the same experiment as in (a), but the NPs were added first followed by addition of valinomycin (300 s). After the initial small polarization caused by NPs themselves, the membrane is polarized further upon addition of valinomycin. Note that after further polarization to an onset overpotential depolarization occurs as in (a) and (b). (d) Overpotentials for the onset of depolarization (black) and final potentials after depolarization (red) as a function of saturation membrane potential given by the potassium ion gradient (Figure S5).
Figure 4
Figure 4. Current–voltage responses in potential step experiments on free-standing phospholipid bilayer membranes. (a) Current traces in response to potential steps of −80/+80 mV. The electrochemical cells are color coded underneath. Note that the largest currents are obtained in the presence of steep gradients of potassium and sodium concentrations across the membrane. (b) I–V curves corresponding to (a). Each point represents the steady-state current of the potential step experiment. The graph has been corrected to eliminate a small offset current (3–4 pA) that is present even in the absence of NPs. The intercept of +8 mV shows that K+ is preferentially transported over Na+. (c,d) Same as (a) and (b) but using sodium and magnesium instead. The intercept at −40 mV shows that sodium is transported preferentially to magnesium. This selectivity also indicates that simple defect formation in the membrane can be excluded as a transport mechanism.
Figure 5
Figure 5. (a) Polarization with potassium gradient after addition of valinomycin. Addition of Au/carborane NPs does not lead to depolarization if magnesium is chosen as the partitioning ion. (b) Same as (a) but the Au/carborane NPs were added before addition of valinomycin at 300 s. Again no depolarization occurs. (c) Polarization with potassium gradient after addition of valinomycin and attempt to further polarize the membrane using Au/carborane NPs as a transporter and sodium as partitioning ion. (d) Same as (c) but the NPs were added before of addition of valinomycin. All electrolyte concentrations are given in the insets.
Figure 6
Figure 6. Scheme of membrane depolarization by transport of sodium and potassium ions. (I) Particles are added to the sodium rich dispersion of vesicles and adsorb to the vesicle membrane (Figure S8). Note, the membrane has been polarized (outside positive) by the presence of a potassium ion concentration gradient and the potassium specific carrier valinomycin (not shown). (II) As the particles penetrate the membrane, sodium ions are released inside the vesicle (down their concentration gradient). (III) As long as particles reside within the membrane, they can shuttle sodium ions across by passive transport down their concentration gradient. In parallel with the mechanism provided by valinomycin, the particles could also contribute to the export of potassium. The process stops when the concentrations of sodium and potassium inside and outside the vesicles are equal. The remaining potential of the depolarized membrane is then due to the partitioning of the anionic nanoparticles.
References
ARTICLE SECTIONSThis article references 33 other publications.
- 1Hamill, O. P.; Marty, A.; Neher, E.; Sakmann, B.; Sigworth, F. J. Improved Patch-Clamp Techniques for High-Resolution Current Recording from Cells and Cell-Free Membrane Patches Pfluegers Arch. 1981, 391, 85– 100 DOI: 10.1007/BF00656997[Crossref], [PubMed], [CAS], Google Scholar1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaL38%252FjslWrug%253D%253D&md5=c981295f57b3239ca3719093b059f44dImproved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patchesHamill O P; Marty A; Neher E; Sakmann B; Sigworth F JPflugers Archiv : European journal of physiology (1981), 391 (2), 85-100 ISSN:0031-6768.1. The extracellular patch clamp method, which first allowed the detection of single channel currents in biological membranes, has been further refined to enable higher current resolution, direct membrane patch potential control, and physical isolation of membrane patches. 2. A description of a convenient method for the fabrication of patch recording pipettes is given together with procedures followed to achieve giga-seals i.e. pipette-membrane seals with resistances of 10(9) - 10(11) omega. 3. The basic patch clamp recording circuit, and designs for improved frequency response are described along with the present limitations in recording the currents from single channels. 4. Procedures for preparation and recording from three representative cell types are given. Some properties of single acetylcholine-activated channels in muscle membrane are described to illustrate the improved current and time resolution achieved with giga-seals. 5. A description is given of the various ways that patches of membrane can be physically isolated from cells. This isolation enables the recording of single channel currents with well-defined solutions on both sides of the membrane. Two types of isolated cell-free patch configurations can be formed: an inside-out patch with its cytoplasmic membrane face exposed to the bath solution, and an outside-out patch with its extracellular membrane face exposed to the bath solution. 6. The application of the method for the recording of ionic currents and internal dialysis of small cells is considered. Single channel resolution can be achieved when recording from whole cells, if the cell diameter is small (less than 20 micrometer). 7. The wide range of cell types amenable to giga-seal formation is discussed.
- 2Neher, E.; Sakmann, B. Single-Channel Currents Recorded from Membrane of Denervated Frog Muscle Fibres Nature 1976, 260, 799– 802 DOI: 10.1038/260799a0[Crossref], [PubMed], [CAS], Google Scholar2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaE287nsVGhtA%253D%253D&md5=f88eb7e304314635339f9ede4f7a4827Single-channel currents recorded from membrane of denervated frog muscle fibresNeher E; Sakmann BNature (1976), 260 (5554), 799-802 ISSN:0028-0836.There is no expanded citation for this reference.
- 3Doyle, D. A.; Morais Cabral, J.; Pfuetzner, R. A.; Kuo, A.; Gulbis, J. M.; Cohen, S. L.; Chait, B. T.; MacKinnon, R. The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity Science 1998, 280, 69– 77 DOI: 10.1126/science.280.5360.69[Crossref], [PubMed], [CAS], Google Scholar3https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXitlWksrY%253D&md5=1656f2dd67f573c8a9bce42cd06bd5beThe structure of the potassium channel: molecular basis of K+ conduction and selectivityDoyle, Declan A.; Cabral, Joao Morais; Pfuetzner, Richard A.; Kuo, Anling; Gulbis, Jacqueline M.; Cohen, Steven L.; Chait, Brian T.; MacKinnon, RoderickScience (Washington, D. C.) (1998), 280 (5360), 69-77CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)A review with 34 refs. The K+ channel from Streptomyces lividans is an integral membrane protein with sequence similarity to all known K+ channels, particularly in the pore region. X-ray anal. with data to 3.2 Å reveals that 4 identical subunits create an inverted teepee, or cone, cradling the selectivity filter of the pore in its outer end. The narrow selectivity filter is only 12 Å long, whereas the remainder of the pore is wider and lined with hydrophobic amino acids. A large water-filled cavity and helix dipoles are positioned so as to overcome electrostatic destabilization of an ion in the pore at the center of the bilayer. The main-chain carbonyl O atoms from the K+ channel signature sequence line the selectivity filter, which is held open by structural constraints to coordinate K+ ions but not smaller Na+ ions. The selectivity filter contains 2 K+ ions ∼7.5 Å apart. This configuration promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between K+ ions and the selectivity filter. The architecture of the pore establishes the phys. principles underlying selective K+ conduction.
- 4Dutzler, R.; Campbell, E. B.; Cadene, M.; Chait, B. T.; MacKinnon, R. X-Ray Structure of a ClC Chloride Channel at 3.0 Å Reveals the Molecular Basis of Anion Selectivity Nature 2002, 415, 287– 294 DOI: 10.1038/415287a[Crossref], [PubMed], [CAS], Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XptlWksA%253D%253D&md5=2f966e52e8f9ab532d1e65d1661b9a15X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivityDutzler, Raimund; Campbell, Ernest B.; Cadene, Martine; Chait, Brian T.; MacKinnon, RoderlelcNature (London, United Kingdom) (2002), 415 (6869), 287-294CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)The ClC Cl- channels catalyze the selective flow of Cl- ions across cell membranes, thereby regulating elec. excitation in skeletal muscle and the flow of salt and water across epithelial barriers. Genetic defects in ClC Cl- channels underlie several familial muscle and kidney diseases. Here, the authors present the x-ray crystal structures of 2 prokaryotic ClC Cl- channels from Salmonella enterica serovar typhimurium and Escherichia coli at 3.0 and 3.5 Å, resp. Both structures revealed 2 identical pores, each pore being formed by a sep. subunit contained within a homodimeric membrane protein. Individual subunits were composed of 2 roughly repeated halves that spanned the membrane with opposite orientations. This antiparallel architecture defined a selectivity filter in which a Cl- ion was stabilized by electrostatic interactions with α-helix dipoles and by chem. coordination with N atoms and OH groups. These findings provide a structural basis for further understanding the function of ClC Cl- channels, and establish the phys. and chem. basis of their anion selectivity.
- 5Yeagle, P. L. Membrane Transport. In The Membranes of Cells, 3rd ed.; Yeagle, P. L., Ed.; Academic Press: Boston, MA, 2016; pp 335– 378.
- 6Stein, W. D.; Litman, T. Carrier-Mediated Transport: Facilitated Disfusion. In Channels, Carriers, and Pumps: An Introduction to Membrane Transport, 2nd ed.; Stein, W. D.; Litman, T., Eds.; Elsevier: London, 2015; pp 131– 178.
- 7Davies, M. Concept Underlie Models. In Functions of Biological Membranes; Chapman & Hall: London, 1973; pp 27– 54.
- 8Petty, H. R. Bioenergetics: Putting Membranes to Work. In Molecular Biology of Membranes: Structure and Function; Springer: New York, 1993; pp 123– 188.
- 9Ghadiri, M. R.; Granja, J. R.; Buehler, L. K. Artificial Transmembrane Ion Channels from Self-Assembling Peptide Nanotubes Nature 1994, 369, 301– 304 DOI: 10.1038/369301a0[Crossref], [PubMed], [CAS], Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXlsleit7k%253D&md5=f895d679b881bb5dada23e22afb4aa9cArtificial transmembrane ion channels from self-assembling peptide nanotubesGhadiri, M. Reza; Granja, Juan R.; Buehler, Lukas K.Nature (London, United Kingdom) (1994), 369 (6478), 301-4CODEN: NATUAS; ISSN:0028-0836.Naturally occurring membrane channels and pores are formed from a large family of diverse proteins, peptides and org. secondary metabolites whose vital biol. functions include control of ion flow, signal transduction, mol. transport and prodn. of cellular toxins. But despite the availability of a large amt. of biochem. information about these mols., the design and synthesis of artificial systems that can mimic the biol. function of natural compds. remains a formidable task. Here the authors present a simple strategy for the design of artificial membrane ion channels based on a self-assembled cylindrical β-sheet peptide architecture. The authors' systems-essentially stacks of peptide rings-display good channel-mediated ion-transport activity with rates exceeding 107 ions s-1, rivalling the performance of many naturally occurring counterparts. Such mol. assemblies should find use in the design of novel cytotoxic agents, membrane transport vehicles and drug-delivery systems.
- 10Fyles, T. M.; Loock, D.; Zhou, X. A Voltage-Gated Ion Channel Based on a Bis-Macrocyclic Bolaamphiphile J. Am. Chem. Soc. 1998, 120, 2997– 3003 DOI: 10.1021/ja972648q[ACS Full Text], [CAS], Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXhslyqsr0%253D&md5=2871d4db4c17b3b0ef2bda7976342abfA Voltage-Gated Ion Channel Based on a Bis-Macrocyclic BolaamphiphileFyles, T. M.; Loock, D.; Zhou, X.Journal of the American Chemical Society (1998), 120 (13), 2997-3003CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The synthesis and characterization of dissym. bis-macrocyclic bolaamphiphile ion channel I is described. Bilayer-clamp expts. give rectified macroscopic current-voltage responses in which current is carried only at cis-neg. potentials. Voltage and orientation-dependent irregular single-channel activity is also obsd. Partial protonation of the carboxylate headgroups of the bolaamphiphile results in long-lived single channels with addnl. shorter-lived states of higher conductance. Single channels are also stabilized in the presence of barium cations. Vesicle expts. establish that transport activity is strongly cation- and concn.-dependent, suggesting the formation of aggregates. The voltage-gating process apparently involves the interaction of the applied potential with the mol. dipole of the bolaamphiphile which stabilizes an active aggregate.
- 11Fyles, T. M. Synthetic Ion Channels in Bilayer Membranes Chem. Soc. Rev. 2007, 36, 335– 347 DOI: 10.1039/B603256G[Crossref], [PubMed], [CAS], Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtVKltbs%253D&md5=f18cf7b363a2ec3f7d8b61901027369fSynthetic ion channels in bilayer membranesFyles, Thomas M.Chemical Society Reviews (2007), 36 (2), 335-347CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Natural ion channels are large protein complexes that regulate key functions of cells. Supramol. chemists have been able to take hints from Nature to design and prep. completely synthetic ion channel systems that reproduce many of the fundamental functions of natural channels. This tutorial review introduces the field to non-specialists. It examines the design, synthesis, incorporation, and characterization of synthetic ion channels in bilayer membranes, and points to potential applications of synthetic ion channels.
- 12Langecker, M.; Arnaut, V.; Martin, T. G.; List, J.; Renner, S.; Mayer, M.; Dietz, H.; Simmel, F. C. Synthetic Lipid Membrane Channels Formed by Designed DNA Nanostructures Science 2012, 338, 932– 936 DOI: 10.1126/science.1225624[Crossref], [PubMed], [CAS], Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhs1GntL7O&md5=0988ffed136b4b1e7364327bde438c8fSynthetic Lipid Membrane Channels Formed by Designed DNA NanostructuresLangecker, Martin; Arnaut, Vera; Martin, Thomas G.; List, Jonathan; Renner, Stephan; Mayer, Michael; Dietz, Hendrik; Simmel, Friedrich C.Science (Washington, DC, United States) (2012), 338 (6109), 932-936CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)We created nanometer-scale transmembrane channels in lipid bilayers by means of self-assembled DNA-based nanostructures. Scaffolded DNA origami was used to create a stem that penetrated and spanned a lipid membrane, as well as a barrel-shaped cap that adhered to the membrane, in part via 26 cholesterol moieties. In single-channel electrophysiol. measurements, we found similarities to the response of natural ion channels, such as conductances on the order of 1 nanosiemens and channel gating. More pronounced gating was seen for mutations in which a single DNA strand of the stem protruded into the channel. Single-mol. translocation expts. show that the synthetic channels can be used to discriminate single DNA mols.
- 13Burns, J. R.; Seifert, A.; Fertig, N.; Howorka, S. A Biomimetic DNA-Based Channel for the Ligand-Controlled Transport of Charged Molecular Cargo across a Biological Membrane Nat. Nanotechnol. 2016, 11, 152– 156 DOI: 10.1038/nnano.2015.279[Crossref], [PubMed], [CAS], Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xns1ajtw%253D%253D&md5=532b1d0a5d1fdd47a02a2c5b3d697f28A biomimetic DNA-based channel for the ligand-controlled transport of charged molecular cargo across a biological membraneBurns, Jonathan R.; Seifert, Astrid; Fertig, Niels; Howorka, StefanNature Nanotechnology (2016), 11 (2), 152-156CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)Biol. ion channels are mol. gatekeepers that control transport across cell membranes. Recreating the functional principle of such systems and extending it beyond physiol. ionic cargo is both scientifically exciting and technol. relevant to sensing or drug release. However, fabricating synthetic channels with a predictable structure remains a significant challenge. Here, we use DNA as a building material to create an atomistically detd. mol. valve that can control when and which cargo is transported across a bilayer. The valve, which is made from seven concatenated DNA strands, can bind a specific ligand and, in response, undergo a nanomech. change to open up the membrane-spanning channel. It is also able to distinguish with high selectivity the transport of small org. mols. that differ by the presence of a pos. or neg. charged group. The DNA device could be used for controlled drug release and the building of synthetic cell-like or logic ionic networks.
- 14Howorka, S. Building Membrane Nanopores Nat. Nanotechnol. 2017, 12, 619– 630 DOI: 10.1038/nnano.2017.99[Crossref], [PubMed], [CAS], Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtFensrvJ&md5=5f621778669959fb6ef7bb201f435ad1Building membrane nanoporesHoworka, StefanNature Nanotechnology (2017), 12 (7), 619-630CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)A review. Membrane nanopores, hollow nanoscale barrels that puncture biol. or synthetic membranes, have become powerful tools in chem.- and biosensing and have achieved notable success in portable DNA sequencing. The pores can be self-assembled from a variety of materials, including proteins, peptides, synthetic org. compds. and, more recently, DNA. But which building material is best for which application, and what is the relation between pore structure and function. In this Review, the author critically compares the characteristics of the different building materials and explores the influence of the building material on pore structure, dynamics and function. The future challenges of developing nanopore technol. were also discussed, and it was considered what the next-generation of nanopore structures could be and where further practical applications might emerge.
- 15Maingi, V.; Burns, J. R.; Uusitalo, J. J.; Howorka, S.; Marrink, S. J.; Sansom, M. S. P. Stability and Dynamics of Membrane-Spanning DNA Nanopores Nat. Commun. 2017, 8, 14784– 14796 DOI: 10.1038/ncomms14784[Crossref], [PubMed], [CAS], Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXkslOhtrs%253D&md5=d45e6928601db5818cc7f7f9cb0a838eStability and dynamics of membrane-spanning DNA nanoporesMaingi, Vishal; Burns, Jonathan R.; Uusitalo, Jaakko J.; Howorka, Stefan; Marrink, Siewert J.; Sansom, Mark S. P.Nature Communications (2017), 8 (), 14784CODEN: NCAOBW; ISSN:2041-1723. (Nature Publishing Group)Recently developed DNA-based analogs of membrane proteins have advanced synthetic biol. A fundamental question is how hydrophilic nanostructures reside in the hydrophobic environment of the membrane. Here, we use multiscale mol. dynamics (MD) simulations to explore the structure, stability and dynamics of an archetypical DNA nanotube inserted via a ring of membrane anchors into a phospholipid bilayer. Coarse-grained MD reveals that the lipids reorganize locally to interact closely with the membrane-spanning section of the DNA tube. Steered simulations along the bilayer normal establish the metastable nature of the inserted pore, yielding a force profile with barriers for membrane exit due to the membrane anchors. Atomistic, equil. simulations at two salt concns. confirm the close packing of lipid around of the stably inserted DNA pore and its cation selectivity, while revealing localized structural fluctuations. The wide-ranging and detailed insight informs the design of next-generation DNA pores for synthetic biol. or biomedicine.
- 16Baše, T.; Bastl, Z.; Plzák, Z.; Grygar, T.; Plešek, J.; Carr, M. J.; Malina, V.; Šubrt, J.; Boháček, J.; Večerníková, E.; Kříž, O. Carboranethiol-Modified Gold Surfaces. A Study and Comparison of Modified Cluster and Flat Surfaces Langmuir 2005, 21, 7776– 7785 DOI: 10.1021/la051122d[ACS Full Text], [CAS], Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmtlGrtr4%253D&md5=c44b0e4da8bfe2cfa54eccc03b17af3cCarboranethiol-Modified Gold Surfaces. A Study and Comparison of Modified Cluster and Flat SurfacesBase, Tomas; Bastl, Zdenek; Plzak, Zbynek; Grygar, Tomas; Plesek, Jaromir; Carr, Michael J.; Malina, Vaclav; Subrt, Jan; Bohacek, Jaroslav; Vecernikova, Eva; Kriz, OtomarLangmuir (2005), 21 (17), 7776-7785CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Four different carboranethiol derivs. were used to modify the surfaces of Au nanoparticles and flat Au films. The novel materials engendered from these modifications are extraordinarily stable species with surfaces that support self-assembled monolayers of 1-(HS)-1,2-C2B10H11, 1,2-(HS)2-1,2-C2B10H10, 1,12-(HS)2-1,12-C2B10H10, and 9,12-(HS)2-1,2-C2B10H10, resp. Surprisingly, characterization of these materials revealed that a no. of mols. of the carboranethiol derivs. are incorporated inside the nanoparticles. This structural feature was studied using a no. of techniques, including XPS, UV-visible, and IR spectroscopies. Thermal desorption expts. show that carborane mols. detach and leave the nanoparticle surface mostly as 1,2-C2B10H10 isotopic clusters, leaving S atoms bound to the Au surface. The surfaces of both the Au nanoparticles and the flat Au films are densely packed with carboranethiolate units. One carborane cluster mol. occupies an area of 6 to 7 surface Au atoms of the nanoparticle and 8 surface Au atoms of the flat film. XPS data showed that mols. of 1,12-(HS)2-1,12-C2B10H10 bind to the flat Au surface with only half of the thiol groups due to the steric demands of the icosahedral carborane skeleton. Electrochem. measurements indicate complete coverage of the modified Au surfaces with the carboranethiol mols.
- 17Cioran, A. M.; Musteti, A. D.; Teixidor, F.; Krpetić, Ž.; Prior, I. A.; He, Q.; Kiely, C. J.; Brust, M.; Viñas, C. Mercaptocarborane-Capped Gold Nanoparticles: Electron Pools and Ion Traps with Switchable Hydrophilicity J. Am. Chem. Soc. 2012, 134, 212– 221 DOI: 10.1021/ja203367h[ACS Full Text], [CAS], Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsFKktrnM&md5=810a0b8c776c11cd65c7f19b533c48d8Mercaptocarborane-Capped Gold Nanoparticles: Electron Pools and Ion Traps with Switchable HydrophilicityCioran, Ana M.; Musteti, Ana D.; Teixidor, Francesc; Krpetic, Zeljka; Prior, Ian A.; He, Qian; Kiely, Christopher J.; Brust, Mathias; Vinas, ClaraJournal of the American Chemical Society (2012), 134 (1), 212-221CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A simple single-phase method for the prepn. of ∼2 nm gold nanoparticles capped with mercaptocarborane ligands is introduced. The resultant monolayer protected clusters (MPCs) exhibit redox-dependent soly. and readily phase transfer between water and nonpolar solvents depending on the electronic and ionic charge stored in the metal core and in the ligand shell, resp. The particles and their properties were characterized by high angle annular dark field imaging in a scanning transmission electron microscope, elemental anal., centrifugal particle sizing, UV-visible and FTIR spectroscopy, and TGA and by 1H, 11B, and 7Li NMR spectroscopy. Cellular uptake of the MPCs by HeLa cells was studied by TEM, and the subsequent generation of reactive oxygen species inside the cells was evaluated by confocal fluorescence microscopy. These MPCs qual. showed significant toxicity and the ability to penetrate into most cell compartments with a strong tendency of finally residing inside membranes. Applications in catalysis, electrocatalysis, and biomedicine are envisaged.
- 18Schwartz, J. J.; Mendoza, A. M.; Wattanatorn, N.; Zhao, Y.; Nguyen, V. T.; Spokoyny, A. M.; Mirkin, C. A.; Baše, T.; Weiss, P. S. Surface Dipole Control of Liquid Crystal Alignment J. Am. Chem. Soc. 2016, 138, 5957– 5967 DOI: 10.1021/jacs.6b02026[ACS Full Text], [CAS], Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmtF2lsLc%253D&md5=2514f49df27761cb9e46d38a0f2af9f1Surface Dipole Control of Liquid Crystal AlignmentSchwartz, Jeffrey J.; Mendoza, Alexandra M.; Wattanatorn, Natcha; Zhao, Yuxi; Nguyen, Vinh T.; Spokoyny, Alexander M.; Mirkin, Chad A.; Base, Tomas; Weiss, Paul S.Journal of the American Chemical Society (2016), 138 (18), 5957-5967CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Detailed understanding and control of the intermol. forces that govern mol. assembly are necessary to engineer structure and function at the nanoscale. Liq. crystal (LC) assembly is exceptionally sensitive to surface properties, capable of transducing nanoscale intermol. interactions into a macroscopic optical readout. Self-assembled monolayers (SAMs) modify surface interactions and are known to influence LC alignment. Here, we exploit the different dipole magnitudes and orientations of carboranethiol and -dithiol positional isomers to deconvolve the influence of SAM-LC dipolar coupling from variations in mol. geometry, tilt, and order. Director orientations and anchoring energies are measured for LC cells employing various carboranethiol and -dithiol isomer alignment layers. The normal component of the mol. dipole in the SAM, toward or away from the underlying substrate, was found to det. the in-plane LC director orientation relative to the anisotropy axis of the surface. By using LC alignment as a probe of interaction strength, we elucidate the role of dipolar coupling of mol. monolayers to their environment in detg. mol. orientations. We apply this understanding to advance the engineering of mol. interactions at the nanoscale.
- 19Tonga, G. Y.; Saha, K.; Rotello, V. M. 25th Anniversary Article: Interfacing Nanoparticles and Biology: New Strategies for Biomedicine Adv. Mater. 2014, 26, 359– 370 DOI: 10.1002/adma.201303001[Crossref], [PubMed], [CAS], Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsF2ntb3P&md5=ae15be8a30c3adf99620a1bbfd05ac2225th Anniversary Article: Interfacing Nanoparticles and Biology: New Strategies for BiomedicineTonga, Gulen Yesilbag; Saha, Krishnendu; Rotello, Vincent M.Advanced Materials (Weinheim, Germany) (2014), 26 (3), 359-370CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The exterior surface of nanoparticles (NPs) dictates the behavior of these systems with the outside world. Understanding the interactions of the NP surface functionality with biosystems enables the design and fabrication of effective platforms for therapeutics, diagnostics, and imaging agents. In this review, we highlight the role of chem. in the engineering of nanomaterials, focusing on the fundamental role played by surface chem. in controlling the interaction of NPs with proteins and cells.
- 20Woolley, G.; Kapral, M.; Deber, C. Potential-Sensitive Membrane Association of a Fluorescent Dye FEBS Lett. 1987, 224, 337– 342 DOI: 10.1016/0014-5793(87)80480-5
- 21Si, W.; Li, Z. T.; Hou, J. L. Voltage-Driven Reversible Insertion into and Leaving from a Lipid Bilayer: Tuning Transmembrane Transport of Artificial Channels Angew. Chem., Int. Ed. 2014, 53, 4578– 4581 DOI: 10.1002/anie.201311249[Crossref], [CAS], Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXltFKlurc%253D&md5=1e80843d30560d7f0f5816e2815f06d0Voltage-Driven Reversible Insertion into and Leaving from a Lipid Bilayer: Tuning Transmembrane Transport of Artificial ChannelsSi, Wen; Li, Zhan-Ting; Hou, Jun-LiAngewandte Chemie, International Edition (2014), 53 (18), 4578-4581CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)Three new artificial transmembrane channel mols. have been designed and synthesized by attaching pos. charged Arg-incorporated tripeptide chains to pillar[5]arene. Fluorescent and patch-clamp expts. revealed that voltage can drive the mols. to insert into and leave from a lipid bilayer and thus switch on and off the transport of K+ ions. One of the mols. was found to display antimicrobial activity toward Bacillus subtilis with half maximal inhibitory concn. (IC50) of 10 μM which is comparable to that of natural channel-forming peptide alamethicin.
- 22Newcomb, C. J.; Sur, S.; Ortony, J. H.; Lee, O.-S.; Matson, J. B.; Boekhoven, J.; Yu, J. M.; Schatz, G. C.; Stupp, S. I. Cell Death versus Cell Survival Instructed by Supramolecular Cohesion of Nanostructures Nat. Commun. 2014, 5, 3321 DOI: 10.1038/ncomms4321[Crossref], [PubMed], [CAS], Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2cvlsFOqtg%253D%253D&md5=3baf11f7a1278e14392fb71219011d05Cell death versus cell survival instructed by supramolecular cohesion of nanostructuresNewcomb Christina J; Sur Shantanu; Ortony Julia H; Matson John B; Boekhoven Job; Yu Jeong Min; Lee One-Sun; Schatz George C; Stupp Samuel INature communications (2014), 5 (), 3321 ISSN:.Many naturally occurring peptides containing cationic and hydrophobic domains have evolved to interact with mammalian cell membranes and have been incorporated into materials for non-viral gene delivery, cancer therapy or treatment of microbial infections. Their electrostatic attraction to the negatively charged cell surface and hydrophobic interactions with the membrane lipids enable intracellular delivery or cell lysis. Although the effects of hydrophobicity and cationic charge of soluble molecules on the cell membrane are well known, the interactions between materials with these molecular features and cells remain poorly understood. Here we report that varying the cohesive forces within nanofibres of supramolecular materials with nearly identical cationic and hydrophobic structure instruct cell death or cell survival. Weak intermolecular bonds promote cell death through disruption of lipid membranes, while materials reinforced by hydrogen bonds support cell viability. These findings provide new strategies to design biomaterials that interact with the cell membrane.
- 23Grzelczak, M. P.; Hill, A. P.; Belic, D.; Bradley, D. F.; Kunstmann-Olsen, C.; Brust, M. Design of Artificial Membrane Transporters from Gold Nanoparticles with Controllable Hydrophobicity Faraday Discuss. 2016, 191, 495– 510 DOI: 10.1039/C6FD00037A[Crossref], [PubMed], [CAS], Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XmvFahsbg%253D&md5=950d91fdb51113f33a1870cbf07bfb74Design of artificial membrane transporters from gold nanoparticles with controllable hydrophobicityGrzelczak, Marcin P.; Hill, Alexander P.; Belic, Domagoj; Bradley, Dan F.; Kunstmann-Olsen, Casper; Brust, MathiasFaraday Discussions (2016), 191 (Nanoparticles with Morphological and Functional Anisotropy), 495-510CODEN: FDISE6; ISSN:1359-6640. (Royal Society of Chemistry)Gold nanoparticles with variable hydrophobicity have been prepd. in three different size regimes following established methods. The control of hydrophobicity was achieved by complexation of the 18-crown-6-CH2-thiolate ligand shell with potassium ions. Potassium dependent phase transfer of these particles from dispersion in water to chloroform was demonstrated, and the equil. partitioning of the particles in water-chloroform liq./liq. systems was quantified by optical spectroscopy. The gradual complexation of the ligand shell with potassium ions was further monitored by zeta potential measurements. Potassium dependent insertion of nanoparticles into the phospholipid bilayer membrane of vesicles in aq. dispersion has been demonstrated by cryogenic transmission electron microscopy (cryo-TEM). Nanoparticle-dependent potassium ion transport across the vesicle membrane has been established by monitoring the membrane potential with fluorescence spectroscopy using a potential sensitive dye.
- 24Tsofina, L. M.; Liberman, E. A.; Babakov, A. V. Production of Bimolecular Protein-Lipid Membranes in Aqueous Solution Nature 1966, 212, 681– 683 DOI: 10.1038/212681a0
- 25Holden, M. A.; Needham, D.; Bayley, H. Functional Bionetworks from Nanoliter Water Droplets J. Am. Chem. Soc. 2007, 129, 8650– 8655 DOI: 10.1021/ja072292a[ACS Full Text], [CAS], Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXmsV2ls7c%253D&md5=6968a13bbc0e7ed88ec1f2dd2bd5b961Functional Bionetworks from Nanoliter Water DropletsHolden, Matthew A.; Needham, David; Bayley, HaganJournal of the American Chemical Society (2007), 129 (27), 8650-8655CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The authors form networks from aq. droplets by submerging them in an oil/lipid mixt. When the droplets are joined together, the lipid monolayers surrounding them combine at the interface to form a robust lipid bilayer. Various protein channels and pores can incorporate into the droplet-interface bilayer (DIB), and the application of a potential with electrodes embedded within the droplets allows ionic currents to be driven across the interface and measured. By joining droplets in linear or branched geometries, functional bionetworks can be created. Although the interfaces between neighboring droplets comprise only single lipid bilayers, the structures of the networks are long-lived and robust. Indeed, a single droplet can be "surgically" excised from a network and replaced with a new droplet without rupturing adjacent DIBs. Networks of droplets can be powered with internal "biobatteries" that use ion gradients or the light-driven proton pump bacteriorhodopsin. Besides their interest as coupled protocells, the droplets can be used as devices for ultrastable bilayer recording with greatly reduced electrolyte vol., which will permit their use in rapid screening applications.
- 26Bayley, H.; Cronin, B.; Heron, A.; Holden, M. A.; Hwang, W. L.; Syeda, R.; Thompson, J.; Wallace, M. Droplet Interface Bilayers Mol. BioSyst. 2008, 4, 1191– 1208 DOI: 10.1039/b808893d[Crossref], [PubMed], [CAS], Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhtlOhtb%252FM&md5=9bcd12423de5096c200ed48d2e868c86Droplet interface bilayersBayley, Hagan; Cronin, Brid; Heron, Andrew; Holden, Matthew A.; Hwang, William L.; Syeda, Ruhma; Thompson, James; Wallace, MarkMolecular BioSystems (2008), 4 (12), 1191-1208CODEN: MBOIBW; ISSN:1742-206X. (Royal Society of Chemistry)A review. Droplet interface bilayers (DIBs) provide a superior platform for the biophys. anal. of membrane proteins. The versatile DIBs can also form networks, with features that include built-in batteries and sensors.
- 27Gordillo, G. J.; Krpetić, Z.; Brust, M. Interactions of Gold Nanoparticles with a Phospholipid Monolayer Membrane on Mercury ACS Nano 2014, 8, 6074– 6080 DOI: 10.1021/nn501395e[ACS Full Text], [CAS], Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXptVWrurY%253D&md5=508a20f0ed7bf6b44663f5ed7095d1d3Interactions of Gold Nanoparticles with a Phospholipid Monolayer Membrane on MercuryGordillo, Gabriel J.; Krpetic, Zeljka; Brust, MathiasACS Nano (2014), 8 (6), 6074-6080CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)It is demonstrated that a compact monolayer of 1,2-dioleoyl-sn-glycero-3-phosphocholine adsorbed to a hanging mercury drop electrode can serve as a simple electrochem. model system to study biomembrane penetration by gold nanoparticles. The hydrogen redox-chem. characteristic of ligand-stabilized gold nanoparticles in molecularly close contact with a mercury electrode is used as an indicator of membrane penetration. Results for water-dispersible gold nanoparticles of two different sizes are reported, and comparisons are made with the cellular uptake of the same prepns. of nanoparticles by a common human fibroblast cell line. The exptl. system described here can be used to study physicochem. aspects of membrane penetration in the absence of complex biol. mechanisms, and it could also be a starting point for the development of a test bed for the toxicity of nanomaterials.
- 28Montal, M.; Mueller, P. Formation of Bimolecular Membranes from Lipid Monolayers and a Study of Their Electrical Properties Proc. Natl. Acad. Sci. U. S. A. 1972, 69, 3561– 3566 DOI: 10.1073/pnas.69.12.3561[Crossref], [PubMed], [CAS], Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE3sXmvVGhtA%253D%253D&md5=1593b730b0ddae8a6960806395e644a8Formation of bimolecular membranes from lipid monolayers and a study of their electrical propertiesMontal, M.; Mueller, P.Proceedings of the National Academy of Sciences of the United States of America (1972), 69 (12), 3561-6CODEN: PNASA6; ISSN:0027-8424.Bimol. membranes are formed from 2 lipid monolayers at an air-water interface by the apposition of their hydrocarbon chains when an aperture in a Teflon partition sepg. 2 aq. phases is lowered through the interface. Formation of the membrane is monitored by an increase of the elec. capacity, as measured with a voltage clamp. Elec. resistance of the unmodified membrane is analogous to that of conventional planar bilayers (black lipid membranes) prepd. in the presence of a hydrocarbon solvent, i.e. 106-108 ohm cm2; the resistance can be lowered to values of 103 ohm cm2 by gramicidin, an antibiotic that modifies the conductance only when the membranes are of bimol. thickness. In contrast to the resistance, there is a significant difference between the capacity of bilayers made from monolayers and that of hydrocarbon-contg. bilayers made by phase transition; the av. values are 0.9 and 0.45 μF cm-2, resp. The value of 0.9 μF cm-2 approximates that of biological membranes. Assuming a dielectric constant of 2.1 for the hydrocarbon region, the dielectric thickness, as calculated from a capacity of 0.9 μF cm-2, is 22 Å. This value is 6-10 Å smaller than the actual thickness of the hydrocarbon region of bilayers and cell membranes, as detd. by x-ray diffraction. The difference may be due to a limited penetration of water into the hydrocarbon region near the ester groups that would lower the electrical resistance of this region and reduce the dielectric thickness. Asymmetric membranes have been formed by adjoining 2 lipid monolayers of different chemical compn.
- 29Montal, M. [50] Formation of Bimolecular Membranes from Lipid Monolayers Methods Enzymol. 1974, 32, 545– 554 DOI: 10.1016/0076-6879(74)32053-8
- 30Smith, H. D.; Obenland, C. O.; Papetti, S. A New Series of Organoboranes. IX. The Preparation and Some Reactions of Sulfur-Carborane Derivatives Inorg. Chem. 1966, 5, 1013– 1015 DOI: 10.1021/ic50040a014[ACS Full Text], [CAS], Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF28XktFansr4%253D&md5=2be7cb726e9a6b277864b75e4410864dA new series of organoboranes. IX. The preparation and some reactions of sulfur-carborane derivativesSmith, H. D., Jr.; Obenland, C. O.; Papetti, S.Inorganic Chemistry (1966), 5 (6), 1013-15CODEN: INOCAJ; ISSN:0020-1669.cf. CA 63, 16378h; 64, 17627d. The first examples of S derivs. of o- and n-carborane are reported and the preparative reactions have been extended to include various B-bromocarboranes. Some chem. of these derivs. is described including the prepn. of an inner complex of Ni.
- 31Viñas, C.; Benakki, R.; Teixidor, F.; Casabo, J. Dimethoxyethane as a Solvent for the Synthesis of C-Monosubstituted O-Carborane Derivatives Inorg. Chem. 1995, 34, 3844– 3845 DOI: 10.1021/ic00118a041
- 32Puchkov, M. N.; Vassarais, R. A.; Korepanova, E. A.; Osipov, A. N. Cytochrome c Produces Pores in Cardiolipin-Containing Planar Bilayer Lipid Membranes in the Presence of Hydrogen Peroxide Biochim. Biophys. Acta, Biomembr. 2013, 1828, 208– 212 DOI: 10.1016/j.bbamem.2012.10.002[Crossref], [PubMed], [CAS], Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVKltw%253D%253D&md5=7ca9becad50db25d1efe07ac5b24c7ddCytochrome c produces pores in cardiolipin-containing planar bilayer lipid membranes in the presence of hydrogen peroxidePuchkov, M. N.; Vassarais, R. A.; Korepanova, E. A.; Osipov, A. N.Biochimica et Biophysica Acta, Biomembranes (2013), 1828 (2), 208-212CODEN: BBBMBS; ISSN:0005-2736. (Elsevier B.V.)Interaction of cytochrome c with cardiolipin in the presence of hydrogen peroxide induces peroxidase activity in cytochrome c and the ability to oxidize membrane lipids. These cytochrome c properties play a substantial role in the cytochrome c-mediated apoptotic reactions. In the present study the elec. properties (specific capacitance and integral conductance) of the cardiolipin-contg. asolectin planar bilayer lipid membranes (pBLM) in the presence of cytochrome c and hydrogen peroxide were studied. Cytochrome c interaction with cardiolipin-contg. pBLM in the presence of hydrogen peroxide resulted in the dramatic increase of the conductance, pore prodn., their growth up to 3.5 nm diam. and subsequent membrane destruction. In the absence of hydrogen peroxide cytochrome c demonstrated almost no effect on the membrane capacitance and conductance. The data obtained prove the pivotal role of cytochrome c and membrane lipids in the permeabilization of pBLM. Correlation of apoptotic reactions and cytochrome c-mediated membrane permeability is discussed.
- 33Negishi, Y.; Nobusada, K.; Tsukuda, T. Glutathione-Protected Gold Clusters Revisited: Bridging the Gap between Gold(I)–Thiolate Complexes and Thiolate-Protected Gold Nanocrystals J. Am. Chem. Soc. 2005, 127, 5261– 5270 DOI: 10.1021/ja042218h[ACS Full Text], [CAS], Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXisVGhtr8%253D&md5=a8fcd56538ee94fd3b86a580e2abd683Glutathione-Protected Gold Clusters Revisited: Bridging the Gap between Gold(I)-Thiolate Complexes and Thiolate-Protected Gold NanocrystalsNegishi, Yuichi; Nobusada, Katsuyuki; Tsukuda, TatsuyaJournal of the American Chemical Society (2005), 127 (14), 5261-5270CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Small gold clusters (∼1 nm) protected by mols. of a tripeptide, glutathione (GSH), were prepd. by reductive decompn. of Au(I)-SG polymers at a low temp. and sepd. into a no. of fractions by polyacrylamide gel electrophoresis (PAGE). Chem. compns. of the fractionated clusters detd. previously by electrospray ionization (ESI) mass spectrometry (Negishi, Y. et al. J. Am. Chem. Soc. 2004, 126, 6518) were reassessed by taking advantage of freshly prepd. samples, higher mass resoln., and more accurate mass calibration; the nine smallest components are reassigned to Au10(SG)10, Au15(SG)13, Au18(SG)14, Au22(SG)16, Au22(SG)17, Au25(SG)18, Au29(SG)20, Au33(SG)22, and Au39(SG)24. These assignments were further confirmed by measuring the mass spectra of the isolated Au:S(h-G) clusters, where h-GSH is a homoglutathione. It is proposed that a series of the isolated Au:SG clusters corresponds to kinetically trapped intermediates of the growing Au cores. The relative abundance of the isolated clusters was correlated well with the thermodn. stabilities against unimol. decompn. The electronic structures of the isolated Au:SG clusters were probed by XPS and optical spectroscopy. The Au(4f) XPS spectra illustrate substantial electron donation from the gold cores to the GS ligands in the Au:SG clusters. The optical absorption and photoluminescence spectra indicate that the electronic structures of the Au:SG clusters are well quantized; embryos of the sp band of the bulk gold evolve remarkably depending on the no. of the gold atoms and GS ligands. The comparison of these spectral data with those of sodium Au(I) thiomalate and 1.8 nm Au:SG nanocrystals (NCs) reveals that the subnanometer-sized Au clusters thiolated constitute a distinct class of binary system which lies between the Au(I)-thiolate complexes and thiolate-protected Au NCs.
Supporting Information
Supporting Information
ARTICLE SECTIONSThe Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.7b06600.
Table 1 and Figures S1–S10 as referred to in the text (PDF)
Terms & Conditions
Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.