Nanoparticles Can Wrap Epithelial Cell Membranes and Relocate Them Across the Epithelial Cell LayerClick to copy article linkArticle link copied!
- Iztok UrbančičIztok Urbančič“Jožef Stefan Institute”, Jamova cesta 39, SI-1000 Ljubljana, SloveniaWeatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, United KingdomMore by Iztok Urbančič
- Maja GarvasMaja Garvas“Jožef Stefan Institute”, Jamova cesta 39, SI-1000 Ljubljana, SloveniaJožef Stefan International Postgraduate School, Jamova cesta 39, SI-1000 Ljubljana, SloveniaMore by Maja Garvas
- Boštjan KokotBoštjan Kokot“Jožef Stefan Institute”, Jamova cesta 39, SI-1000 Ljubljana, SloveniaMore by Boštjan Kokot
- Hana MajaronHana Majaron“Jožef Stefan Institute”, Jamova cesta 39, SI-1000 Ljubljana, SloveniaMore by Hana Majaron
- Polona UmekPolona Umek“Jožef Stefan Institute”, Jamova cesta 39, SI-1000 Ljubljana, SloveniaCenter of Excellence NAMASTE, Jamova cesta 39, SI-1000 Ljubljana, SloveniaMore by Polona Umek
- Hilary CassidyHilary CassidySystems Biology Ireland, University College Dublin, Dublin 4, IrelandMore by Hilary Cassidy
- Miha ŠkarabotMiha Škarabot“Jožef Stefan Institute”, Jamova cesta 39, SI-1000 Ljubljana, SloveniaMore by Miha Škarabot
- Falk SchneiderFalk SchneiderWeatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, United KingdomMore by Falk Schneider
- Silvia GalianiSilvia GalianiWeatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, United KingdomMore by Silvia Galiani
- Zoran ArsovZoran Arsov“Jožef Stefan Institute”, Jamova cesta 39, SI-1000 Ljubljana, SloveniaCenter of Excellence NAMASTE, Jamova cesta 39, SI-1000 Ljubljana, SloveniaMore by Zoran Arsov
- Tilen KoklicTilen Koklic“Jožef Stefan Institute”, Jamova cesta 39, SI-1000 Ljubljana, SloveniaCenter of Excellence NAMASTE, Jamova cesta 39, SI-1000 Ljubljana, SloveniaMore by Tilen Koklic
- David MatallanasDavid MatallanasSystems Biology Ireland, University College Dublin, Dublin 4, IrelandSchool of Medicine and Medical Science, University College Dublin, Dublin 4, IrelandMore by David Matallanas
- Miran Čeh
- Igor MuševičIgor Muševič“Jožef Stefan Institute”, Jamova cesta 39, SI-1000 Ljubljana, SloveniaFaculty of Mathematics and Physics, University of Ljubljana, Jadranska 19, SI-1000 Ljubljana, SloveniaMore by Igor Muševič
- Christian EggelingChristian EggelingWeatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, United KingdomInstitute of Applied Optics, Friedrich-Schiller University, Jena 07749, GermanyLeibniz Institute of Photonic Technology (IPHT), Jena 07745, GermanyMore by Christian Eggeling
- Janez Štrancar*Janez Štrancar*Phone: +38614773226. E-mail: [email protected]“Jožef Stefan Institute”, Jamova cesta 39, SI-1000 Ljubljana, SloveniaCenter of Excellence NAMASTE, Jamova cesta 39, SI-1000 Ljubljana, SloveniaMore by Janez Štrancar
Abstract
Although the link between the inhalation of nanoparticles and cardiovascular disease is well established, the causal pathway between nanoparticle exposure and increased activity of blood coagulation factors remains unexplained. To initiate coagulation tissue factor bearing epithelial cell membranes should be exposed to blood, on the other side of the less than a micrometre thin air-blood barrier. For the inhaled nanoparticles to promote coagulation, they need to bind lung epithelial-cell membrane parts and relocate them into the blood. To assess this hypothesis, we use advanced microscopy and spectroscopy techniques to show that the nanoparticles wrap themselves with epithelial-cell membranes, leading to the membrane’s disruption. The membrane-wrapped nanoparticles are then observed to freely diffuse across the damaged epithelial cell layer relocating epithelial cell membrane parts over the epithelial layer. Proteomic analysis of the protein content in the nanoparticles wraps/corona finally reveals the presence of the coagulation-initiating factors, supporting the proposed causal link between the inhalation of nanoparticles and cardiovascular disease.
Results and Discussion
Conclusions
Material and Methods
Synthesis of Nanoparticles
Functionalization and Fluorescent Labeling of the NPs
Preparation of Liposomes
FRET FMS Experiments and References
FMS Analysis
TEM
Fluorescence Fluctuation-Based Experiments
Confocal and STED Imaging of LUV and NP
Image Analysis
STED Imaging of LA-4 Cells with NP
Viability Tests
TEM of the Lavage
Proteomics on Wrapped NP
Supporting Information
Supporting Information is available free of charge via the Internet at The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.nanolett.8b02291.
Motivation, material, equipment, preparation of the samples, measurements of zeta-potential, fluorescence microspectrosopy (FMS), dynamic light scattering (DLS), experiments based on fluorescence fluctuations, confocal and STED fluorescence imaging of LUV and NP, fluorescence spectroscopy of NP and LUV, STED imaging of LA-4 cells and NP, lactate dehidrogenase (LDH) assay, cell viability test (hoechst and propidium iodide), determination of plasma membrane fraction used in wrapping of TiO2 nanotubes, proteomic analysis of lipid-protein corona on TiO2 nanotubes, additional comments, references (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.
Acknowledgments
This work was supported by Slovenian Research Agency (program P1-0060), EU Horizon 2020 programme (project SmartNanoTox), ESRR (Centre of Excellence NAMASTE), and Marie Skłodowska-Curie Action (FNS-4-NAMOSAT, I.U.) the MRC (Grant MC_UU_12010/unit programs G0902418 and MC_UU_12025), the Wellcome Trust (Grant 104924/14/Z/14), MRC/BBSRC/EPSRC (Grant MR/K01577X/1), MRC/BBSRC/EPSRC (Grant MR/K01577X/1), the Wolfson Foundation (for initial funding of the Wolfson Imaging Centre Oxford), and Oxford-internal funding (John Fell Fund and EPA Cephalosporin Fund). The authors thank Anže Testen, Anja Dobravec, Katarina van Midden, and David Dolhar for their help with the preparation of the samples and measurements, Prof. Dr. Alenka Mertelj (“Jožef Stefan” Institute, Ljubljana, Slovenia) for access to their DLS instrument and help with experiments, the Wolfson Imaging Centre Oxford (Dominic Waithe and Chris Lagerholm), members of the Laboratory of Biophysics (especially Stane Pajk for providing the environment-sensitive probe) and Nano-Immunology lab (especially Erdinc Sezgin for his help with FCS) as well as the Micron Advanced Imaging Unit (Strategic Award 091911) for support.
NPs | nanoparticles |
FMS | fluorescence microspectroscopy |
STED | stimulated emission depletion |
References
This article references 39 other publications.
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- 15Jackman, J. A.; Zan, G. H.; Zhao, Z.; Cho, N.-J. Contribution of the Hydration Force to Vesicle Adhesion on Titanium Oxide. Langmuir 2014, 30 (19), 5368– 5372, DOI: 10.1021/la404581dGoogle Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXntFOmsbg%253D&md5=34f22c142e23721710fd16891c566647Contribution of the Hydration Force to Vesicle Adhesion on Titanium OxideJackman, Joshua A.; Zan, Goh Haw; Zhao, Zhilei; Cho, Nam-JoonLangmuir (2014), 30 (19), 5368-5372CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Titanium oxide is a biocompatible material that supports vesicle adhesion. Depending on exptl. parameters, adsorbed vesicles remain intact or rupture spontaneously. Vesicle rupture has been attributed to electrostatic attraction between vesicles and titanium oxide, although the relative contribution of various interfacial forces remains to be clarified. Herein, we investigated the influence of vesicle surface charge on vesicle adsorption onto titanium oxide and obsd. that electrostatic attraction is insufficient for vesicle rupture. Following this line of evidence, a continuum model based on the DLVO forces and a non-DLVO hydration force was applied to investigate the role of different interfacial forces in modulating the lipid-substrate interaction. Within an exptl. significant range of conditions, the model shows that the magnitude of the repulsive hydration force strongly influences the behavior of adsorbed vesicles, thereby supporting that the hydration force makes a strong contribution to the fate of adsorbed vesicles on titanium oxide. The findings are consistent with literature reports concerning phospholipid assemblies on solid supports and nanoparticles and underscore the importance of the hydration force in influencing the behavior of phospholipid films on hydrophilic surfaces.
- 16Schleh, C.; Mühlfeld, C.; Pulskamp, K.; Schmiedl, A.; Nassimi, M.; Lauenstein, H. D.; Braun, A.; Krug, N.; Erpenbeck, V. J.; Hohlfeld, J. M. The Effect of Titanium Dioxide Nanoparticles on Pulmonary Surfactant Function and Ultrastructure. Respir. Res. 2009, 10, 90, DOI: 10.1186/1465-9921-10-90Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1MjgvVKrug%253D%253D&md5=2b2537a834ae1d4a165fe6d10bb707beThe effect of titanium dioxide nanoparticles on pulmonary surfactant function and ultrastructureSchleh Carsten; Muhlfeld Christian; Pulskamp Karin; Schmiedl Andreas; Nassimi Matthias; Lauenstein Hans D; Braun Armin; Krug Norbert; Erpenbeck Veit J; Hohlfeld Jens MRespiratory research (2009), 10 (), 90 ISSN:.BACKGROUND: Pulmonary surfactant reduces surface tension and is present at the air-liquid interface in the alveoli where inhaled nanoparticles preferentially deposit. We investigated the effect of titanium dioxide (TiO(2)) nanosized particles (NSP) and microsized particles (MSP) on biophysical surfactant function after direct particle contact and after surface area cycling in vitro. In addition, TiO(2) effects on surfactant ultrastructure were visualized. METHODS: A natural porcine surfactant preparation was incubated with increasing concentrations (50-500 microg/ml) of TiO(2) NSP or MSP, respectively. Biophysical surfactant function was measured in a pulsating bubble surfactometer before and after surface area cycling. Furthermore, surfactant ultrastructure was evaluated with a transmission electron microscope. RESULTS: TiO(2) NSP, but not MSP, induced a surfactant dysfunction. For TiO(2) NSP, adsorption surface tension (gammaads) increased in a dose-dependent manner from 28.2 + or - 2.3 mN/m to 33.2 + or - 2.3 mN/m (p < 0.01), and surface tension at minimum bubble size (gammamin) slightly increased from 4.8 + or - 0.5 mN/m up to 8.4 + or - 1.3 mN/m (p < 0.01) at high TiO(2) NSP concentrations. Presence of NSP during surface area cycling caused large and significant increases in both gammaads (63.6 + or - 0.4 mN/m) and gammamin (21.1 + or - 0.4 mN/m). Interestingly, TiO(2) NSP induced aberrations in the surfactant ultrastructure. Lamellar body like structures were deformed and decreased in size. In addition, unilamellar vesicles were formed. Particle aggregates were found between single lamellae. CONCLUSION: TiO(2) nanosized particles can alter the structure and function of pulmonary surfactant. Particle size and surface area respectively play a critical role for the biophysical surfactant response in the lung.
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- 18Yamashita, K.; Yoshioka, Y.; Higashisaka, K.; Mimura, K.; Morishita, Y.; Nozaki, M.; Yoshida, T.; Ogura, T.; Nabeshi, H.; Nagano, K. Silica and Titanium Dioxide Nanoparticles Cause Pregnancy Complications in Mice. Nat. Nanotechnol. 2011, 6 (5), 321– 328, DOI: 10.1038/nnano.2011.41Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXls1Kgsrg%253D&md5=285d4d761ce8bccf578c7e3b4d26bb7dSilica and titanium dioxide nanoparticles cause pregnancy complications in miceYamashita, Kohei; Yoshioka, Yasuo; Higashisaka, Kazuma; Mimura, Kazuya; Morishita, Yuki; Nozaki, Masatoshi; Yoshida, Tokuyuki; Ogura, Toshinobu; Nabeshi, Hiromi; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Monobe, Youko; Imazawa, Takayoshi; Aoshima, Hisae; Shishido, Kiyoshi; Kawai, Yuichi; Mayumi, Tadanori; Tsunoda, Shin-ichi; Itoh, Norio; Yoshikawa, Tomoaki; Yanagihara, Itaru; Saito, Shigeru; Tsutsumi, YasuoNature Nanotechnology (2011), 6 (5), 321-328CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)The increasing use of nanomaterials has raised concerns about their potential risks to human health. Recent studies have shown that nanoparticles can cross the placenta barrier in pregnant mice and cause neurotoxicity in their offspring, but a more detailed understanding of the effects of nanoparticles on pregnant animals remains elusive. Here, we show that silica and titanium dioxide nanoparticles with diams. of 70 nm and 35 nm, resp., can cause pregnancy complications when injected i.v. into pregnant mice. The silica and titanium dioxide nanoparticles were found in the placenta, fetal liver and fetal brain. Mice treated with these nanoparticles had smaller uteri and smaller fetuses than untreated controls. Fullerene mols. and larger (300 and 1,000 nm) silica particles did not induce these complications. These detrimental effects are linked to structural and functional abnormalities in the placenta on the maternal side, and are abolished when the surfaces of the silica nanoparticles are modified with carboxyl and amine groups.
- 19Garvas, M.; Testen, A.; Umek, P.; Gloter, A.; Koklic, T.; Strancar, J. Protein Corona Prevents TiO2 Phototoxicity. PLoS One 2015, 10 (6), e0129577, DOI: 10.1371/journal.pone.0129577Google ScholarThere is no corresponding record for this reference.
- 20Urbančič, I.; Arsov, Z.; Ljubetič, A.; Biglino, D.; Strancar, J. Bleaching-Corrected Fluorescence Microspectroscopy with Nanometer Peak Position Resolution. Opt. Express 2013, 21 (21), 25291– 25306, DOI: 10.1364/OE.21.025291Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXltlegtbk%253D&md5=1ad2f2c82f791ebb810160f2ce2fbac8Bleaching-corrected fluorescence microspectroscopy with nanometer peak position resolutionUrbancic, Iztok; Arsov, Zoran; Ljubetic, Ajasja; Biglino, Daniele; Strancar, JanezOptics Express (2013), 21 (21), 25291/1-25291/16CODEN: OPEXFF; ISSN:1094-4087. (Optical Society of America)Fluorescence microspectroscopy (FMS) with environmentally sensitive dyes provides information about local mol. surroundings at microscopic spatial resoln. Until recently, only probes exhibiting large spectral shifts due to local changes have been used. For filter-based exptl. systems, where signal at different wavelengths is acquired sequentially, photostability has been required in addn. Herein, we systematically analyzed our spectral fitting models and bleaching correction algorithms which mitigate both limitations. We showed that careful anal. of data acquired by stochastic wavelength sampling enables nanometer spectral peak position resoln. even for highly photosensitive fluorophores. To demonstrate how small spectral shifts and changes in bleaching rates can be exploited, we analyzed vesicles in different lipid phases. Our findings suggest that a wide range of dyes, commonly used in bulk spectrofluorimetry but largely avoided in microspectroscopy due to the above-mentioned restrictions, can be efficiently applied also in FMS.
- 21Urbančič, I.; Ljubetič, A.; Arsov, Z.; Štrancar, J. Coexistence of Probe Conformations in Lipid Phases—a Polarized Fluorescence Microspectroscopy Study. Biophys. J. 2013, 105 (4), 919– 927, DOI: 10.1016/j.bpj.2013.07.005Google ScholarThere is no corresponding record for this reference.
- 22Arsov, Z.; Urbančič, I.; Štrancar, J. Aggregation-Induced Emission Spectral Shift as a Measure of Local Concentration of a pH-Activatable Rhodamine-Based Smart Probe. Spectrochim. Acta, Part A 2018, 190, 486, DOI: 10.1016/j.saa.2017.09.067Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsFyltLnK&md5=55dd3fcb7da7bbf66cf8b396f6e0e2c2Aggregation-induced emission spectral shift as a measure of local concentration of a pH-activatable rhodamine-based smart probeArsov, Zoran; Urbancic, Iztok; Strancar, JanezSpectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy (2018), 190 (), 486-493CODEN: SAMCAS; ISSN:1386-1425. (Elsevier B.V.)Generating activatable probes that report about mol. vicinity through contact-based mechanisms such as aggregation can be very convenient. Specifically, such probes change a particular spectral property only at the intended biol. relevant target. Xanthene derivs., for example rhodamines, are able to form aggregates. It is typical to examine aggregation by absorption spectroscopy but for microscopy applications using fluorescent probes it is very important to perform characterization by measuring fluorescence spectra. First excitation spectra of aq. solns. of rhodamine 6G can be very informative about the aggregation features. Next the authors establish the dependence of the fluorescence emission spectral max. shift on the dimer concn. The obtained information helped one confirm the possibility of aggregation of a recently designed and synthesized rhodamine 6G-based pH-activatable fluorescent probe and to study its pH and concn. dependence. The size of the aggregation-induced emission spectral shift at specific position on the sample can be measured by fluorescence microspectroscopy, which at particular pH allows estn. of the local concn. of the obsd. probe at microscopic level. Therefore, besides aggregation-caused quenching and aggregation-induced emission also aggregation-induced emission spectral shift can be a useful photophys. phenomenon.
- 23Wang, F.; Liu, J. A Stable Lipid/TiO2 Interface with Headgroup-Inversed Phosphocholine and a Comparison with SiO2. J. Am. Chem. Soc. 2015, 137 (36), 11736– 11742, DOI: 10.1021/jacs.5b06642Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtlOqu7fM&md5=67a2f3e311080dc9f99ce16cdbca17fdA Stable Lipid/TiO2 Interface with Headgroup-Inversed Phosphocholine and a Comparison with SiO2Wang, Feng; Liu, JuewenJournal of the American Chemical Society (2015), 137 (36), 11736-11742CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Zwitterionic phosphocholine (PC) lipids are highly biocompatible, representing a major component of the cell membrane. A simple mixing of PC liposomes and silica (SiO2) surface results in liposome fusion with the surface and formation of supported lipid bilayers. However, the stability of this bilayer is relatively low because adsorption is based mainly on weak van der Waals force. PC lipids strongly adsorb by TiO2 via chem. bonding with the lipid phosphate. The lack of fusion on TiO2 is attributable to the steric effect from the choline group in PC. Inverse phosphocholine lipids (CP) were used, directly exposing the phosphate. Using a calcein leakage assay and cryo-TEM, fusion of CP liposome with TiO2 is demonstrated. The stability of this supported bilayer is significantly higher than that of the PC/SiO2 system, as indicated by washing the membrane under harsh conditions. Adsorption of CP liposomes by TiO2 is inhibited at high pH. The CP liposome cannot fuse with silica surface because of a strong charge repulsion. This study demonstrates an interesting interplay between a soft matter surface and metal oxides. By tuning the lipid structure, it is possible to rationally control the interaction force. This study provides an alternative system for forming stable supported bilayers on TiO2, and represents the first example of interfacing inverse lipids with inorg. surfaces.
- 24Haustein, E.; Schwille, P. Ultrasensitive Investigations of Biological Systems by Fluorescence Correlation Spectroscopy. Methods 2003, 29 (2), 153– 166, DOI: 10.1016/S1046-2023(02)00306-7Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXhsVajsb0%253D&md5=8b02f84d480bfba7fa10135813ac088aUltrasensitive investigations of biological systems by fluorescence correlation spectroscopyHaustein, Elke; Schwille, PetraMethods (San Diego, CA, United States) (2003), 29 (2), 153-166CODEN: MTHDE9; ISSN:1046-2023. (Elsevier Science)A review. Fluorescence correlation spectroscopy (FCS) exts. information about mol. dynamics from the tiny fluctuations that can be obsd. in the emission of small ensembles of fluorescent mols. in thermodn. equil. Employing a confocal setup in conjunction with highly dil. samples, the av. no. of fluorescent particles simultaneously within the measurement vol. (∼1 fl) is minimized. Among the multitude of chem. and phys. parameters accessible by FCS are local concns., mobility coeffs., rate consts. for assocn. and dissocn. processes, and even enzyme kinetics. As any reaction causing an alteration of the primary measurement parameters such as fluorescence brightness or mobility can be monitored, the application of this noninvasive method to unravel processes in living cells is straightforward. Due to the high spatial resoln. of less than 0.5 μm, selective measurements in cellular compartments, e.g., to probe receptor-ligand interactions on cell membranes, are feasible. Moreover, the observation of local mol. dynamics provides access to environmental parameters such as local oxygen concns., pH, or viscosity. Thus, this versatile technique is of particular attractiveness for researchers striving for quant. assessment of interactions and dynamics of small mol. quantities in biol. relevant systems.
- 25Bacia, K.; Kim, S. A.; Schwille, P. Fluorescence Cross-Correlation Spectroscopy in Living Cells. Nat. Methods 2006, 3 (2), 83, DOI: 10.1038/nmeth822Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xmtl2ktQ%253D%253D&md5=6c7fd793a454b90f42e30ed4f44b8c19Fluorescence cross-correlation spectroscopy in living cellsBacia, Kirsten; Kim, Sally A.; Schwille, PetraNature Methods (2006), 3 (2), 83-89CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)A review. Cell biologists strive to characterize mol. interactions directly in the intracellular environment. The intrinsic resoln. of optical microscopy, however, allows visualization of only coarse subcellular localization. By extg. information from mol. dynamics, fluorescence cross-correlation spectroscopy (FCCS) grants access to processes on a mol. scale, such as diffusion, binding, enzymic reactions and codiffusion, and has become a valuable tool for studies in living cells. Here we review basic principles of FCCS and focus on seminal applications, including examples of intracellular signaling and trafficking. We consider FCCS in the context of fluorescence resonance energy transfer and multicolor imaging techniques and discuss application strategies and recent tech. advances.
- 26Winkler, T.; Kettling, U.; Koltermann, A.; Eigen, M. Confocal Fluorescence Coincidence Analysis: An Approach to Ultra High-Throughput Screening. Proc. Natl. Acad. Sci. U. S. A. 1999, 96 (4), 1375– 1378, DOI: 10.1073/pnas.96.4.1375Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXhsFSrtbk%253D&md5=c377ac7ca0178f70cbbcf58137ad8b41Confocal fluorescence coincidence analysis: an approach to ultra high-throughput screeningWinkler, Thorsten; Kettling, Ulrich; Koltermann, Andre; Eigen, ManfredProceedings of the National Academy of Sciences of the United States of America (1999), 96 (4), 1375-1378CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Fluorescence-based assay technologies play an increasing role in high-throughput screening. They can be classified into different categories: fluorescence polarization, time-resolved fluorescence, fluorescence resonance energy transfer, and fluorescence correlation spectroscopy. In this work we present an alternative anal. technique for high-throughput screening, which we call confocal fluorescence coincidence anal. Confocal fluorescence coincidence anal. exts. fluorescence fluctuations that occur coincidently in two different spectral ranges from a tiny observation vol. of below 1 fl. This procedure makes it possible to monitor whether an assocn. between mol. fragments that are labeled with different fluorophores is established or broken. Therefore, it provides access to the characterization of a variety of cleavage and ligation reactions in biochem. Confocal fluorescence coincidence anal. is a very sensitive and ultrafast technique with readout times of 100 ms and below. This feature is demonstrated by means of a homogeneous assay for restriction endonuclease EcoRI. The presented achievements break ground for throughput rates as high as 106 samples per day with using only small amts. of sample substance and therefore constitute a solid base for screening applications in drug discovery and evolutionary biotechnol.
- 27Li, Y.; Gu, N. Thermodynamics of Charged Nanoparticle Adsorption on Charge-Neutral Membranes: A Simulation Study. J. Phys. Chem. B 2010, 114 (8), 2749– 2754, DOI: 10.1021/jp904550bGoogle Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhvVKitbg%253D&md5=cca79491b6f97e60da240c5885a71d63Thermodynamics of Charged Nanoparticle Adsorption on Charge-Neutral Membranes: A Simulation StudyLi, Yang; Gu, NingJournal of Physical Chemistry B (2010), 114 (8), 2749-2754CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)The interactions between charged nanoparticles (NPs) and charge-neutral phospholipid membranes are investigated by coarse-grained mol. dynamics simulations. Three kinds of nanoparticles are modeled with different surface charge densities: the uncharged one, the pos. charged one, and the neg. charged one. We find that the electrostatic attraction improves the adhesion of a charged nanoparticle to the membrane. With the increase of electrostatic energy, a charged NP can be almost fully wrapped by the membrane. In addn., analyses of structural variations suggest that the adhesion of a charged NP induces a local transition in fluid bilayers. Some thermodn. quantities such as free energy, entropy, and enthalpy are also obtained to explain the process of NPs binding. Furthermore, the bending energy of wrapping of NPs against the electrostatic potential energy is also discussed based on the Helfrich theory, indicating that the driving force of the wrap originates from the gain in electrostatic energy at the cost of the elastic energy of biomembranes. Our observations shed light on the origin of expts. of the wrap as well as the mechanism of structural transitions of membranes due to the electrostatic binding.
- 28Wang, B.; Zhang, L.; Bae, S. C.; Granick, S. Nanoparticle-Induced Surface Reconstruction of Phospholipid Membranes. Proc. Natl. Acad. Sci. U. S. A. 2008, 105 (47), 18171– 18175, DOI: 10.1073/pnas.0807296105Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhsVOmsb%252FP&md5=1b3d6555f4aea996fc460ede6c837c3bNanoparticle-induced surface reconstruction of phospholipid membranesWang, Bo; Zhang, Liangfang; Bae, Sung Chul; Granick, SteveProceedings of the National Academy of Sciences of the United States of America (2008), 105 (47), 18171-18175, S18171/1-S18171/5CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)The nonspecific adsorption of charged nanoparticles onto single-component phospholipid bilayers bearing phosphocholine headgroups is shown, from fluorescence and calorimetry expts., to cause surface reconstruction at the points where nanoparticles adsorb. Nanoparticles of neg. charge induce local gelation in otherwise fluid bilayers; nanoparticles of pos. charge induce otherwise gelled membranes to fluidize locally. Through this mechanism, the phase state deviates from the nominal phase transition temp. by tens of degrees. This work generalizes the notions of environmentally induced surface reconstruction, prominent in metals and semiconductors. Bearing in mind that chem. compn. in these single-component lipid bilayers is the same everywhere, this offers a mechanism to generate patchy functional properties in phospholipid membranes.
- 29Ruf, W. FXa Takes Center Stage in Vascular Inflammation. Blood 2014, 123 (11), 1630– 1631, DOI: 10.1182/blood-2014-02-553081Google ScholarThere is no corresponding record for this reference.
- 30Cirino, G.; Cicala, C.; Bucci, M.; Sorrentino, L.; Ambrosini, G.; DeDominicis, G.; Altieri, D. C. Factor Xa as an Interface between Coagulation and Inflammation. Molecular Mimicry of Factor Xa Association with Effector Cell Protease Receptor-1 Induces Acute Inflammation in Vivo. J. Clin. Invest. 1997, 99 (10), 2446– 2451, DOI: 10.1172/JCI119428Google ScholarThere is no corresponding record for this reference.
- 31Brook, R. D.; Franklin, B.; Cascio, W.; Hong, Y.; Howard, G.; Lipsett, M.; Luepker, R.; Mittleman, M.; Samet, J.; Smith, S. C. Air Pollution and Cardiovascular Disease: A Statement for Healthcare Professionals From the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation 2004, 109 (21), 2655– 2671, DOI: 10.1161/01.CIR.0000128587.30041.C8Google ScholarThere is no corresponding record for this reference.
- 32Wang, F.; Yu, L.; Monopoli, M. P.; Sandin, P.; Mahon, E.; Salvati, A.; Dawson, K. A. The Biomolecular Corona Is Retained during Nanoparticle Uptake and Protects the Cells from the Damage Induced by Cationic Nanoparticles until Degraded in the Lysosomes. Nanomedicine 2013, 9 (8), 1159– 1168, DOI: 10.1016/j.nano.2013.04.010Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFSmtLnJ&md5=226fb91b5b40f2306ff904035e02a095The biomolecular corona is retained during nanoparticle uptake and protects the cells from the damage induced by cationic nanoparticles until degraded in the lysosomesWang, Fengjuan; Yu, Lu; Monopoli, Marco P.; Sandin, Peter; Mahon, Eugene; Salvati, Anna; Dawson, Kenneth A.Nanomedicine (New York, NY, United States) (2013), 9 (8), 1159-1168CODEN: NANOBF; ISSN:1549-9634. (Elsevier)Nanoparticles have unique capacities of interacting with the cellular machinery and entering cells. To be able to exploit this potential, it is essential to understand what controls the interactions at the interface between nanoparticles and cells: it is now established that nanoparticles in biol. media are covered by proteins and other biomols. forming a "corona" on the nanoparticle surface, which confers a new identity to the nanoparticles. By labeling the proteins of the serum, using pos.-charged polystyrene, we now show that this adsorbed layer is strong enough to be retained on the nanoparticles as they enter cells and is trafficked to the lysosomes on the nanoparticles. There, the corona is degraded and this is followed by lysosomal damage, leading to cytosolic release of lysosomal content, and ultimately apoptosis. Thus the corona protects the cells from the damage induced by the bare nanoparticle surface until enzymically cleared in the lysosomes. This study investigates the effects of protein corona that normally forms on the surface of nanoparticles during in vivo use, describing the steps of intracellular processing of such particles, to enhance our understanding of how these particles interact with the cellular machinery.
- 33Jimeno-Romero, A.; Oron, M.; Cajaraville, M. P.; Soto, M.; Marigómez, I. Nanoparticle Size and Combined Toxicity of TiO2 and DSLS (Surfactant) Contribute to Lysosomal Responses in Digestive Cells of Mussels Exposed to TiO2 Nanoparticles. Nanotoxicology 2016, 10 (8), 1168– 1176, DOI: 10.1080/17435390.2016.1196250Google ScholarThere is no corresponding record for this reference.
- 34Zhu, Y.; Eaton, J. W.; Li, C. Titanium Dioxide (TiO2) Nanoparticles Preferentially Induce Cell Death in Transformed Cells in a Bak/Bax-Independent Fashion. PLoS One 2012, 7 (11), e50607, DOI: 10.1371/journal.pone.0050607Google ScholarThere is no corresponding record for this reference.
- 35Anguissola, S.; Garry, D.; Salvati, A.; O’Brien, P. J.; Dawson, K. A. High Content Analysis Provides Mechanistic Insights on the Pathways of Toxicity Induced by Amine-Modified Polystyrene Nanoparticles. PLoS One 2014, 9 (9), e108025, DOI: 10.1371/journal.pone.0108025Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslSisr7J&md5=0f6e608a4c656c70b471a69098d4a311High content analysis provides mechanistic insights on the pathways of toxicity induced by amine-modified polystyrene nanoparticlesAnguissola, Sergio; Garry, David; Salvati, Anna; O'Brien, Peter J.; Dawson, Kenneth A.PLoS One (2014), 9 (9), e108025/1-e108025/16, 16 pp.CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)The fast-paced development of nanotechnol. needs the support of effective safety testing. We have developed a screening platform measuring simultaneously several cellular parameters for exposure to various concns. of nanoparticles (NPs). Cell lines representative of different organ cell types, including lung, endothelium, liver, kidney, macrophages, glia, and neuronal cells were exposed to 50 nm amine-modified polystyrene (PS-NH2) NPs previously reported to induce apoptosis and to 50 nm sulfonated and carboxyl-modified polystyrene NPs that were reported to be silent. All cell lines apart from Raw 264.7 executed apoptosis in response to PS-NH2 NPs, showing specific sequences of EC50 thresholds; lysosomal acidification was the most sensitive parameter. Loss of mitochondrial membrane potential and plasma membrane integrity measured by High Content Anal. resulted comparably sensitive to the equiv. OECD-recommended assays, allowing increased output. Anal. of the acidic compartments revealed good cerrelation between size/fluorescence intensity and dose of PS-NH2 NPs applied; moreover steatosis and phospholipidosis were obsd., consistent with the lysosomal alterations revealed by Lysotracker green; similar responses were obsd. when comparing astrocytoma cells with primary astrocytes. We have established a platform providing mechanistic insights on the response to exposure to nanoparticles. Such platform holds great potential for in vitro screening of nanomaterials in highthroughput format.
- 36Stern, S. T.; Adiseshaiah, P. P.; Crist, R. M. Autophagy and Lysosomal Dysfunction as Emerging Mechanisms of Nanomaterial Toxicity. Part. Fibre Toxicol. 2012, 9, 20, DOI: 10.1186/1743-8977-9-20Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFCjurY%253D&md5=11cdb360401c2abf5759ced2cc60e352Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicityStern, Stephan T.; Adiseshaiah, Pavan P.; Crist, Rachael M.Particle and Fibre Toxicology (2012), 9 (), 20CODEN: PFTABQ; ISSN:1743-8977. (BioMed Central Ltd.)The study of the potential risks assocd. with the manuf., use, and disposal of nanoscale materials, and their mechanisms of toxicity, is important for the continued advancement of nanotechnol. Currently, the most widely accepted paradigms of nanomaterial toxicity are oxidative stress and inflammation, but the underlying mechanisms are poorly defined. This review will highlight the significance of autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Most endocytic routes of nanomaterial cell uptake converge upon the lysosome, making the lysosomal compartment the most common intracellular site of nanoparticle sequestration and degrdn. In addn. to the endo-lysosomal pathway, recent evidence suggests that some nanomaterials can also induce autophagy. Among the many physiol. functions, the lysosome, by way of the autophagy (macroautophagy) pathway, degrades intracellular pathogens, and damaged organelles and proteins. Thus, autophagy induction by nanoparticles may be an attempt to degrade what is perceived by the cell as foreign or aberrant. While the autophagy and endo-lysosomal pathways have the potential to influence the disposition of nanomaterials, there is also a growing body of literature suggesting that biopersistent nanomaterials can, in turn, neg. impact these pathways. Indeed, there is ample evidence that biopersistent nanomaterials can cause autophagy and lysosomal dysfunctions resulting in toxicol. consequences.
- 37Umek, P.; Korošec, R. C.; Jančar, B.; Dominko, R.; Arčon, D. The Influence of the Reaction Temperature on the Morphology of Sodium Titanate 1D Nanostructures and Their Thermal Stability. J. Nanosci. Nanotechnol. 2007, 7 (10), 3502– 3508, DOI: 10.1166/jnn.2007.838Google ScholarThere is no corresponding record for this reference.
- 38Akashi, K.; Miyata, H.; Itoh, H.; Kinosita, K. Preparation of Giant Liposomes in Physiological Conditions and Their Characterization under an Optical Microscope. Biophys. J. 1996, 71 (6), 3242– 3250, DOI: 10.1016/S0006-3495(96)79517-6Google ScholarThere is no corresponding record for this reference.
- 39Cox, J.; Hein, M. Y.; Luber, C. A.; Paron, I.; Nagaraj, N.; Mann, M. Accurate Proteome-Wide Label-Free Quantification by Delayed Normalization and Maximal Peptide Ratio Extraction, Termed MaxLFQ. Mol. Cell. Proteomics 2014, 13 (9), 2513– 2526, DOI: 10.1074/mcp.M113.031591Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVynurrI&md5=f3f1c7dc8fbf729c568446968b89f37cAccurate Proteome-wide Label-free Quantification by Delayed Normalization and Maximal Peptide Ratio Extraction, Termed MaxLFQCox, Juergen; Hein, Marco Y.; Luber, Christian A.; Paron, Igor; Nagaraj, Nagarjuna; Mann, MatthiasMolecular & Cellular Proteomics (2014), 13 (9), 2513-2526CODEN: MCPOBS; ISSN:1535-9484. (American Society for Biochemistry and Molecular Biology)Protein quantification without isotopic labels has been a long-standing interest in the proteomics field. However, accurate and robust proteome-wide quantification with label-free approaches remains a challenge. We developed a new intensity detn. and normalization procedure called MaxLFQ that is fully compatible with any peptide or protein sepn. prior to LC-MS anal. Protein abundance profiles are assembled using the max. possible information from MS signals, given that the presence of quantifiable peptides varies from sample to sample. For a benchmark dataset with two proteomes mixed at known ratios, we accurately detected the mixing ratio over the entire protein expression range, with greater precision for abundant proteins. The significance of individual label-free quantifications was obtained via a t test approach. For a second benchmark dataset, we accurately quantify fold changes over several orders of magnitude, a task that is challenging with label-based methods. MaxLFQ is a generic label-free quantification technol. that is readily applicable to many biol. questions; it is compatible with std. statistical anal. workflows, and it has been validated in many and diverse biol. projects. Our algorithms can handle very large expts. of 500+ samples in a manageable computing time. It is implemented in the freely available MaxQuant computational proteomics platform and works completely seamlessly at the click of a button.
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- 4Miller, M. R.; Raftis, J. B.; Langrish, J. P.; McLean, S. G.; Samutrtai, P.; Connell, S. P.; Wilson, S.; Vesey, A. T.; Fokkens, P. H. B.; Boere, A. J. F. Inhaled Nanoparticles Accumulate at Sites of Vascular Disease. ACS Nano 2017, 11 (5), 4542– 4552, DOI: 10.1021/acsnano.6b085514https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmsFCjurY%253D&md5=e425e3f6ce34680e73525b3cdbf8d4ceInhaled Nanoparticles Accumulate at Sites of Vascular DiseaseMiller, Mark R.; Raftis, Jennifer B.; Langrish, Jeremy P.; McLean, Steven G.; Samutrtai, Pawitrabhorn; Connell, Shea P.; Wilson, Simon; Vesey, Alex T.; Fokkens, Paul H. B.; Boere, A. John F.; Krystek, Petra; Campbell, Colin J.; Hadoke, Patrick W. F.; Donaldson, Ken; Cassee, Flemming R.; Newby, David E.; Duffin, Rodger; Mills, Nicholas L.ACS Nano (2017), 11 (5), 4542-4552CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The development of engineered nanomaterials is growing exponentially, despite concerns over their potential similarities to environmental nanoparticles that are assocd. with significant cardiorespiratory morbidity and mortality. The mechanisms through which inhalation of nanoparticles could trigger acute cardiovascular events are emerging, but a fundamental unanswered question remains; do inhaled nanoparticles translocate from the lung in man and directly contribute to the pathogenesis of cardiovascular disease. In complementary clin. and exptl. studies, the authors used gold nanoparticles to evaluate particle translocation, permitting detection by high-resoln. inductively coupled mass spectrometry and Raman microscopy. Healthy volunteers were exposed to nanoparticles by acute inhalation, followed by repeated sampling of blood and urine. Gold was detected in the blood and urine within 15 min -24 h after exposure, and was still present 3 mo after exposure. Levels were greater following inhalation of 5 nm (primary diam.) particles compared to 30 nm particles. Studies in mice demonstrated the accumulation in the blood and liver following pulmonary exposure to a broader size range of gold nanoparticles (2-200 nm primary diam.), with translocation markedly greater for particles <10 nm diam. Gold nanoparticles preferentially accumulated in inflammation-rich vascular lesions of fat-fed apolipoprotein E-deficient mice. Furthermore, following inhalation, gold particles could be detected in surgical specimens of carotid artery disease from patients at risk of stroke. Translocation of inhaled nanoparticles into the systemic circulation and accumulation at sites of vascular inflammation provides a direct mechanism that can explain the link between environmental nanoparticles and cardiovascular disease, and has major implications for risk management in the use of engineered nanomaterials.
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- 7U.S. EPA National Center for Environmental Assessment, R. T. P. N.; Sacks, J. Provisional Assessment of Recent Studies on Health Effects of Particulate Matter Exposure https://cfpub.epa.gov/ncea/isa/recordisplay.cfm?deid=247132 (accessed Nov 5, 2017).There is no corresponding record for this reference.
- 8Drake, T. A.; Morrissey, J. H.; Edgington, T. S. Selective Cellular Expression of Tissue Factor in Human Tissues. Implications for Disorders of Hemostasis and Thrombosis. Am. J. Pathol. 1989, 134 (5), 1087– 10978https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaL1M3ksVyqsw%253D%253D&md5=2b5f03cac1119a68cd9d12d042ffa4f5Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosisDrake T A; Morrissey J H; Edgington T SThe American journal of pathology (1989), 134 (5), 1087-97 ISSN:0002-9440.Tissue factor (TF), the primary cellular initiator of the coagulation protease cascade, is implicated in having important roles in hemostasis, thrombogenesis, inflammation, and the cellular immune response, although the cytologic distribution of TF in tissues has yet to be described. This study used epitope-defined monoclonal antibodies to human tissue factor for immunohistochemical localization of TF in normal human tissues. TF was selectively expressed in tissues and was associated with cells rather than extracellular matrix. It was anatomically sequestered from blood, being undetectable in endothelium and peripheral blood cells. TF was present in vascular adventitia, organ capsules, epidermis, and mucosal epithelium. Most dermal and submucosal fibroblasts were negative. Except for alveolar macrophages and possibly dendritic cells of some lymphoid follicles, tissue macrophages did not express TF; (expression was demonstrable in LPS stimulated monocytes). Cerebral cortex, renal glomeruli, and cardiac myocytes were additional sites of prominent TF expression. Based on the cellular distribution of TF, it is hypothesized that intravascular initiation of coagulation requires induced expression by intravascular cells, and that the normal distribution of TF represents a hemostatic "envelope" ready to activate coagulation when vascular integrity is disrupted.
- 9Hoffman, M.; Monroe, D. M. A Cell-Based Model of Hemostasis. Thromb. Haemostasis 2001, 85 (6), 958– 965, DOI: 10.1055/s-0037-16159479https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXlt1GhtLo%253D&md5=d52a05c18b9b0eadcf86064f4cb421a6A cell-based model of hemostasisHoffman, Maureane; Monroe, Dougald M., IIIThrombosis and Haemostasis (2001), 85 (6), 958-965CODEN: THHADQ; ISSN:0340-6245. (Schattauer GmbH)A review, with 61 refs. Based on our work and that of many other workers, we have developed a model of coagulation in vivo. Many workers have demonstrated mechanisms by which cells can influence the coagulation process. Nonetheless, the prevailing view of hemostasis remains that the protein coagulation factors direct and control the process with cells serving primarily to provide a phosphatidylserine-contg. surface on which the procoagulant complexes are assembled. By contrast, we propose a model in which coagulation is regulated by properties of cell surfaces. This model emphasizes the importance of specific cellular receptors for the coagulation proteins. Thus, cells with similar phosphatidylserine content can play very different roles in hemostasis depending on their complement of surface receptors. We propose that coagulation occurs not as a cascade, but in 3 overlapping stages: (1) initiation, which occurs on a tissue factor bearing cell; (2) amplification, in which platelets and cofactors are activated to set the stage for large scale thrombin generation; and (3) propagation, in which large amts. of thrombin are generated on the platelet surface. This cell based model explains some aspects of hemostasis that a protein-centric model does not.
- 10Liu, J. Interfacing Zwitterionic Liposomes with Inorganic Nanomaterials: Surface Forces, Membrane Integrity, and Applications. Langmuir 2016, 32 (18), 4393– 4404, DOI: 10.1021/acs.langmuir.6b0049310https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xmt12ntLs%253D&md5=ddd5d3d1ec51ed0a02f9b62bc1c6b54dInterfacing Zwitterionic Liposomes with Inorganic Nanomaterials: Surface Forces, Membrane Integrity, and ApplicationsLiu, JuewenLangmuir (2016), 32 (18), 4393-4404CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Zwitterionic phosphocholine (PC) lipids are the main constituent of the mammalian cell membrane. PC bilayers are known for their antifouling properties, yet they are adsorbed by all tested inorg. nanoparticles. This feature article is focused on the developments in my lab. in the past few years on this topic. The main exptl. techniques include fluorescence-based liposome leakage assays, adsorption and desorption, and cryo-TEM. Different materials interact with PC liposomes differently. PC liposomes adsorb on SiO2, followed by membrane fusion with the surface forming supported lipid bilayers. TiO2 and other metal oxides adsorb only intact PC liposomes via lipid phosphate bonding; the steric effect from the choline group hinders subsequent liposome fusion onto the particles. Citrate-capped AuNPs are adsorbed very strongly via van der Waals forces, inducing local gelation. The result is transient liposome leakage upon AuNP adsorption or desorption and AuNP aggregation on the liposome surface. All carbon-based nanomaterials (graphene oxides, carbon nanotubes, and nanodiamond) are adsorbed mainly via hydrogen bonding. The oxidn. level of graphene oxide strongly influences the outcome of the final hybrid material. In the context of inorg. nanoparticle adsorption, insights are given regarding the lack of protein adsorption by PC bilayers. These inorg./lipid hybrid materials can be used for controlled release, drug delivery, and fundamental studies. A few examples of application are covered toward the end, and future perspectives are given.
- 11Hu, Q.; Bai, X.; Hu, G.; Zuo, Y. Y. Unveiling the Molecular Structure of Pulmonary Surfactant Corona on Nanoparticles. ACS Nano 2017, 11, 6832, DOI: 10.1021/acsnano.7b0187311https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXosVOrtLc%253D&md5=8dc5eadd3e1c9cc53163aa3e989bfc49Unveiling the molecular structure of pulmonary surfactant corona on nanoparticlesHu, Qinglin; Bai, Xuan; Hu, Guoqing; Zuo, Yi Y.ACS Nano (2017), 11 (7), 6832-6842CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)The growing risk of human exposure to airborne nanoparticles (NPs) causes a general concern on the biosafety of nanotechnol. Inhaled NPs can deposit in the deep lung at which they interact with the pulmonary surfactant (PS). Despite the increasing study of nano-bio interactions, detailed mol. mechanisms by which inhaled NPs interact with the natural PS system remain unclear. Using coarse-grained mol. dynamics simulation, we studied the interaction between NPs and the PS system in the alveolar fluid. It was found that regardless of different physicochem. properties, upon contacting the PS, both silver and polystyrene NPs are immediately coated with a biomol. corona that consists of both lipids and proteins. Structure and mol. conformation of the PS corona depend on the hydrophobicity of the pristine NPs. Quant. anal. revealed that lipid compn. of the corona formed on different NPs is relatively conserved and is similar to that of the bulk phase PS. However, relative abundance of the surfactant-assocd. proteins, SP-A, SP-B, and SP-C, is notably affected by the hydrophobicity of the NP. The PS corona provides the NPs with a physicochem. barrier against the environment, equalizes the hydrophobicity of the pristine NPs, and may enhance biorecognition of the NPs. These modifications in physicochem. properties may play a crucial role in affecting the biol. identity of the NPs and hence alter their subsequent interactions with cells and other biol. entities. Our results suggest that all studies of inhalation nanotoxicol. or NP-based pulmonary drug delivery should consider the influence of the PS corona.
- 12Pera, H.; Nolte, T. M.; Leermakers, F. A. M.; Kleijn, J. M. Coverage and Disruption of Phospholipid Membranes by Oxide Nanoparticles. Langmuir 2014, 30 (48), 14581– 14590, DOI: 10.1021/la503413wThere is no corresponding record for this reference.
- 13Alkhammash, H. I.; Li, N.; Berthier, R.; de Planque, M. R. R. Native Silica Nanoparticles Are Powerful Membrane Disruptors. Phys. Chem. Chem. Phys. 2015, 17 (24), 15547– 15560, DOI: 10.1039/C4CP05882HThere is no corresponding record for this reference.
- 14Fortunelli, A.; Monti, S. Simulations of Lipid Adsorption on TiO2 Surfaces in Solution. Langmuir 2008, 24 (18), 10145– 10154, DOI: 10.1021/la801787sThere is no corresponding record for this reference.
- 15Jackman, J. A.; Zan, G. H.; Zhao, Z.; Cho, N.-J. Contribution of the Hydration Force to Vesicle Adhesion on Titanium Oxide. Langmuir 2014, 30 (19), 5368– 5372, DOI: 10.1021/la404581d15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXntFOmsbg%253D&md5=34f22c142e23721710fd16891c566647Contribution of the Hydration Force to Vesicle Adhesion on Titanium OxideJackman, Joshua A.; Zan, Goh Haw; Zhao, Zhilei; Cho, Nam-JoonLangmuir (2014), 30 (19), 5368-5372CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Titanium oxide is a biocompatible material that supports vesicle adhesion. Depending on exptl. parameters, adsorbed vesicles remain intact or rupture spontaneously. Vesicle rupture has been attributed to electrostatic attraction between vesicles and titanium oxide, although the relative contribution of various interfacial forces remains to be clarified. Herein, we investigated the influence of vesicle surface charge on vesicle adsorption onto titanium oxide and obsd. that electrostatic attraction is insufficient for vesicle rupture. Following this line of evidence, a continuum model based on the DLVO forces and a non-DLVO hydration force was applied to investigate the role of different interfacial forces in modulating the lipid-substrate interaction. Within an exptl. significant range of conditions, the model shows that the magnitude of the repulsive hydration force strongly influences the behavior of adsorbed vesicles, thereby supporting that the hydration force makes a strong contribution to the fate of adsorbed vesicles on titanium oxide. The findings are consistent with literature reports concerning phospholipid assemblies on solid supports and nanoparticles and underscore the importance of the hydration force in influencing the behavior of phospholipid films on hydrophilic surfaces.
- 16Schleh, C.; Mühlfeld, C.; Pulskamp, K.; Schmiedl, A.; Nassimi, M.; Lauenstein, H. D.; Braun, A.; Krug, N.; Erpenbeck, V. J.; Hohlfeld, J. M. The Effect of Titanium Dioxide Nanoparticles on Pulmonary Surfactant Function and Ultrastructure. Respir. Res. 2009, 10, 90, DOI: 10.1186/1465-9921-10-9016https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1MjgvVKrug%253D%253D&md5=2b2537a834ae1d4a165fe6d10bb707beThe effect of titanium dioxide nanoparticles on pulmonary surfactant function and ultrastructureSchleh Carsten; Muhlfeld Christian; Pulskamp Karin; Schmiedl Andreas; Nassimi Matthias; Lauenstein Hans D; Braun Armin; Krug Norbert; Erpenbeck Veit J; Hohlfeld Jens MRespiratory research (2009), 10 (), 90 ISSN:.BACKGROUND: Pulmonary surfactant reduces surface tension and is present at the air-liquid interface in the alveoli where inhaled nanoparticles preferentially deposit. We investigated the effect of titanium dioxide (TiO(2)) nanosized particles (NSP) and microsized particles (MSP) on biophysical surfactant function after direct particle contact and after surface area cycling in vitro. In addition, TiO(2) effects on surfactant ultrastructure were visualized. METHODS: A natural porcine surfactant preparation was incubated with increasing concentrations (50-500 microg/ml) of TiO(2) NSP or MSP, respectively. Biophysical surfactant function was measured in a pulsating bubble surfactometer before and after surface area cycling. Furthermore, surfactant ultrastructure was evaluated with a transmission electron microscope. RESULTS: TiO(2) NSP, but not MSP, induced a surfactant dysfunction. For TiO(2) NSP, adsorption surface tension (gammaads) increased in a dose-dependent manner from 28.2 + or - 2.3 mN/m to 33.2 + or - 2.3 mN/m (p < 0.01), and surface tension at minimum bubble size (gammamin) slightly increased from 4.8 + or - 0.5 mN/m up to 8.4 + or - 1.3 mN/m (p < 0.01) at high TiO(2) NSP concentrations. Presence of NSP during surface area cycling caused large and significant increases in both gammaads (63.6 + or - 0.4 mN/m) and gammamin (21.1 + or - 0.4 mN/m). Interestingly, TiO(2) NSP induced aberrations in the surfactant ultrastructure. Lamellar body like structures were deformed and decreased in size. In addition, unilamellar vesicles were formed. Particle aggregates were found between single lamellae. CONCLUSION: TiO(2) nanosized particles can alter the structure and function of pulmonary surfactant. Particle size and surface area respectively play a critical role for the biophysical surfactant response in the lung.
- 17Setyawati, M. I.; Tay, C. Y.; Chia, S. L.; Goh, S. L.; Fang, W.; Neo, M. J.; Chong, H. C.; Tan, S. M.; Loo, S. C. J.; Ng, K. W. Titanium Dioxide Nanomaterials Cause Endothelial Cell Leakiness by Disrupting the Homophilic Interaction of VE-Cadherin. Nat. Commun. 2013, 4, 1673, DOI: 10.1038/ncomms265517https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3srktleisA%253D%253D&md5=5673cc211ec4630b316d296f177249c1Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE-cadherinSetyawati M I; Tay C Y; Chia S L; Goh S L; Fang W; Neo M J; Chong H C; Tan S M; Loo S C J; Ng K W; Xie J P; Ong C N; Tan N S; Leong D TNature communications (2013), 4 (), 1673 ISSN:.The use of nanomaterials has raised safety concerns, as their small size facilitates accumulation in and interaction with biological tissues. Here we show that exposure of endothelial cells to TiO2 nanomaterials causes endothelial cell leakiness. This effect is caused by the physical interaction between TiO2 nanomaterials and endothelial cells' adherens junction protein VE-cadherin. As a result, VE-cadherin is phosphorylated at intracellular residues (Y658 and Y731), and the interaction between VE-cadherin and p120 as well as β-catenin is lost. The resulting signalling cascade promotes actin remodelling, as well as internalization and degradation of VE-cadherin. We show that injections of TiO2 nanomaterials cause leakiness of subcutaneous blood vessels in mice and, in a melanoma-lung metastasis mouse model, increase the number of pulmonary metastases. Our findings uncover a novel non-receptor-mediated mechanism by which nanomaterials trigger intracellular signalling cascades via specific interaction with VE-cadherin, resulting in nanomaterial-induced endothelial cell leakiness.
- 18Yamashita, K.; Yoshioka, Y.; Higashisaka, K.; Mimura, K.; Morishita, Y.; Nozaki, M.; Yoshida, T.; Ogura, T.; Nabeshi, H.; Nagano, K. Silica and Titanium Dioxide Nanoparticles Cause Pregnancy Complications in Mice. Nat. Nanotechnol. 2011, 6 (5), 321– 328, DOI: 10.1038/nnano.2011.4118https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXls1Kgsrg%253D&md5=285d4d761ce8bccf578c7e3b4d26bb7dSilica and titanium dioxide nanoparticles cause pregnancy complications in miceYamashita, Kohei; Yoshioka, Yasuo; Higashisaka, Kazuma; Mimura, Kazuya; Morishita, Yuki; Nozaki, Masatoshi; Yoshida, Tokuyuki; Ogura, Toshinobu; Nabeshi, Hiromi; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Monobe, Youko; Imazawa, Takayoshi; Aoshima, Hisae; Shishido, Kiyoshi; Kawai, Yuichi; Mayumi, Tadanori; Tsunoda, Shin-ichi; Itoh, Norio; Yoshikawa, Tomoaki; Yanagihara, Itaru; Saito, Shigeru; Tsutsumi, YasuoNature Nanotechnology (2011), 6 (5), 321-328CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)The increasing use of nanomaterials has raised concerns about their potential risks to human health. Recent studies have shown that nanoparticles can cross the placenta barrier in pregnant mice and cause neurotoxicity in their offspring, but a more detailed understanding of the effects of nanoparticles on pregnant animals remains elusive. Here, we show that silica and titanium dioxide nanoparticles with diams. of 70 nm and 35 nm, resp., can cause pregnancy complications when injected i.v. into pregnant mice. The silica and titanium dioxide nanoparticles were found in the placenta, fetal liver and fetal brain. Mice treated with these nanoparticles had smaller uteri and smaller fetuses than untreated controls. Fullerene mols. and larger (300 and 1,000 nm) silica particles did not induce these complications. These detrimental effects are linked to structural and functional abnormalities in the placenta on the maternal side, and are abolished when the surfaces of the silica nanoparticles are modified with carboxyl and amine groups.
- 19Garvas, M.; Testen, A.; Umek, P.; Gloter, A.; Koklic, T.; Strancar, J. Protein Corona Prevents TiO2 Phototoxicity. PLoS One 2015, 10 (6), e0129577, DOI: 10.1371/journal.pone.0129577There is no corresponding record for this reference.
- 20Urbančič, I.; Arsov, Z.; Ljubetič, A.; Biglino, D.; Strancar, J. Bleaching-Corrected Fluorescence Microspectroscopy with Nanometer Peak Position Resolution. Opt. Express 2013, 21 (21), 25291– 25306, DOI: 10.1364/OE.21.02529120https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXltlegtbk%253D&md5=1ad2f2c82f791ebb810160f2ce2fbac8Bleaching-corrected fluorescence microspectroscopy with nanometer peak position resolutionUrbancic, Iztok; Arsov, Zoran; Ljubetic, Ajasja; Biglino, Daniele; Strancar, JanezOptics Express (2013), 21 (21), 25291/1-25291/16CODEN: OPEXFF; ISSN:1094-4087. (Optical Society of America)Fluorescence microspectroscopy (FMS) with environmentally sensitive dyes provides information about local mol. surroundings at microscopic spatial resoln. Until recently, only probes exhibiting large spectral shifts due to local changes have been used. For filter-based exptl. systems, where signal at different wavelengths is acquired sequentially, photostability has been required in addn. Herein, we systematically analyzed our spectral fitting models and bleaching correction algorithms which mitigate both limitations. We showed that careful anal. of data acquired by stochastic wavelength sampling enables nanometer spectral peak position resoln. even for highly photosensitive fluorophores. To demonstrate how small spectral shifts and changes in bleaching rates can be exploited, we analyzed vesicles in different lipid phases. Our findings suggest that a wide range of dyes, commonly used in bulk spectrofluorimetry but largely avoided in microspectroscopy due to the above-mentioned restrictions, can be efficiently applied also in FMS.
- 21Urbančič, I.; Ljubetič, A.; Arsov, Z.; Štrancar, J. Coexistence of Probe Conformations in Lipid Phases—a Polarized Fluorescence Microspectroscopy Study. Biophys. J. 2013, 105 (4), 919– 927, DOI: 10.1016/j.bpj.2013.07.005There is no corresponding record for this reference.
- 22Arsov, Z.; Urbančič, I.; Štrancar, J. Aggregation-Induced Emission Spectral Shift as a Measure of Local Concentration of a pH-Activatable Rhodamine-Based Smart Probe. Spectrochim. Acta, Part A 2018, 190, 486, DOI: 10.1016/j.saa.2017.09.06722https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsFyltLnK&md5=55dd3fcb7da7bbf66cf8b396f6e0e2c2Aggregation-induced emission spectral shift as a measure of local concentration of a pH-activatable rhodamine-based smart probeArsov, Zoran; Urbancic, Iztok; Strancar, JanezSpectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy (2018), 190 (), 486-493CODEN: SAMCAS; ISSN:1386-1425. (Elsevier B.V.)Generating activatable probes that report about mol. vicinity through contact-based mechanisms such as aggregation can be very convenient. Specifically, such probes change a particular spectral property only at the intended biol. relevant target. Xanthene derivs., for example rhodamines, are able to form aggregates. It is typical to examine aggregation by absorption spectroscopy but for microscopy applications using fluorescent probes it is very important to perform characterization by measuring fluorescence spectra. First excitation spectra of aq. solns. of rhodamine 6G can be very informative about the aggregation features. Next the authors establish the dependence of the fluorescence emission spectral max. shift on the dimer concn. The obtained information helped one confirm the possibility of aggregation of a recently designed and synthesized rhodamine 6G-based pH-activatable fluorescent probe and to study its pH and concn. dependence. The size of the aggregation-induced emission spectral shift at specific position on the sample can be measured by fluorescence microspectroscopy, which at particular pH allows estn. of the local concn. of the obsd. probe at microscopic level. Therefore, besides aggregation-caused quenching and aggregation-induced emission also aggregation-induced emission spectral shift can be a useful photophys. phenomenon.
- 23Wang, F.; Liu, J. A Stable Lipid/TiO2 Interface with Headgroup-Inversed Phosphocholine and a Comparison with SiO2. J. Am. Chem. Soc. 2015, 137 (36), 11736– 11742, DOI: 10.1021/jacs.5b0664223https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtlOqu7fM&md5=67a2f3e311080dc9f99ce16cdbca17fdA Stable Lipid/TiO2 Interface with Headgroup-Inversed Phosphocholine and a Comparison with SiO2Wang, Feng; Liu, JuewenJournal of the American Chemical Society (2015), 137 (36), 11736-11742CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Zwitterionic phosphocholine (PC) lipids are highly biocompatible, representing a major component of the cell membrane. A simple mixing of PC liposomes and silica (SiO2) surface results in liposome fusion with the surface and formation of supported lipid bilayers. However, the stability of this bilayer is relatively low because adsorption is based mainly on weak van der Waals force. PC lipids strongly adsorb by TiO2 via chem. bonding with the lipid phosphate. The lack of fusion on TiO2 is attributable to the steric effect from the choline group in PC. Inverse phosphocholine lipids (CP) were used, directly exposing the phosphate. Using a calcein leakage assay and cryo-TEM, fusion of CP liposome with TiO2 is demonstrated. The stability of this supported bilayer is significantly higher than that of the PC/SiO2 system, as indicated by washing the membrane under harsh conditions. Adsorption of CP liposomes by TiO2 is inhibited at high pH. The CP liposome cannot fuse with silica surface because of a strong charge repulsion. This study demonstrates an interesting interplay between a soft matter surface and metal oxides. By tuning the lipid structure, it is possible to rationally control the interaction force. This study provides an alternative system for forming stable supported bilayers on TiO2, and represents the first example of interfacing inverse lipids with inorg. surfaces.
- 24Haustein, E.; Schwille, P. Ultrasensitive Investigations of Biological Systems by Fluorescence Correlation Spectroscopy. Methods 2003, 29 (2), 153– 166, DOI: 10.1016/S1046-2023(02)00306-724https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXhsVajsb0%253D&md5=8b02f84d480bfba7fa10135813ac088aUltrasensitive investigations of biological systems by fluorescence correlation spectroscopyHaustein, Elke; Schwille, PetraMethods (San Diego, CA, United States) (2003), 29 (2), 153-166CODEN: MTHDE9; ISSN:1046-2023. (Elsevier Science)A review. Fluorescence correlation spectroscopy (FCS) exts. information about mol. dynamics from the tiny fluctuations that can be obsd. in the emission of small ensembles of fluorescent mols. in thermodn. equil. Employing a confocal setup in conjunction with highly dil. samples, the av. no. of fluorescent particles simultaneously within the measurement vol. (∼1 fl) is minimized. Among the multitude of chem. and phys. parameters accessible by FCS are local concns., mobility coeffs., rate consts. for assocn. and dissocn. processes, and even enzyme kinetics. As any reaction causing an alteration of the primary measurement parameters such as fluorescence brightness or mobility can be monitored, the application of this noninvasive method to unravel processes in living cells is straightforward. Due to the high spatial resoln. of less than 0.5 μm, selective measurements in cellular compartments, e.g., to probe receptor-ligand interactions on cell membranes, are feasible. Moreover, the observation of local mol. dynamics provides access to environmental parameters such as local oxygen concns., pH, or viscosity. Thus, this versatile technique is of particular attractiveness for researchers striving for quant. assessment of interactions and dynamics of small mol. quantities in biol. relevant systems.
- 25Bacia, K.; Kim, S. A.; Schwille, P. Fluorescence Cross-Correlation Spectroscopy in Living Cells. Nat. Methods 2006, 3 (2), 83, DOI: 10.1038/nmeth82225https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xmtl2ktQ%253D%253D&md5=6c7fd793a454b90f42e30ed4f44b8c19Fluorescence cross-correlation spectroscopy in living cellsBacia, Kirsten; Kim, Sally A.; Schwille, PetraNature Methods (2006), 3 (2), 83-89CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)A review. Cell biologists strive to characterize mol. interactions directly in the intracellular environment. The intrinsic resoln. of optical microscopy, however, allows visualization of only coarse subcellular localization. By extg. information from mol. dynamics, fluorescence cross-correlation spectroscopy (FCCS) grants access to processes on a mol. scale, such as diffusion, binding, enzymic reactions and codiffusion, and has become a valuable tool for studies in living cells. Here we review basic principles of FCCS and focus on seminal applications, including examples of intracellular signaling and trafficking. We consider FCCS in the context of fluorescence resonance energy transfer and multicolor imaging techniques and discuss application strategies and recent tech. advances.
- 26Winkler, T.; Kettling, U.; Koltermann, A.; Eigen, M. Confocal Fluorescence Coincidence Analysis: An Approach to Ultra High-Throughput Screening. Proc. Natl. Acad. Sci. U. S. A. 1999, 96 (4), 1375– 1378, DOI: 10.1073/pnas.96.4.137526https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXhsFSrtbk%253D&md5=c377ac7ca0178f70cbbcf58137ad8b41Confocal fluorescence coincidence analysis: an approach to ultra high-throughput screeningWinkler, Thorsten; Kettling, Ulrich; Koltermann, Andre; Eigen, ManfredProceedings of the National Academy of Sciences of the United States of America (1999), 96 (4), 1375-1378CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Fluorescence-based assay technologies play an increasing role in high-throughput screening. They can be classified into different categories: fluorescence polarization, time-resolved fluorescence, fluorescence resonance energy transfer, and fluorescence correlation spectroscopy. In this work we present an alternative anal. technique for high-throughput screening, which we call confocal fluorescence coincidence anal. Confocal fluorescence coincidence anal. exts. fluorescence fluctuations that occur coincidently in two different spectral ranges from a tiny observation vol. of below 1 fl. This procedure makes it possible to monitor whether an assocn. between mol. fragments that are labeled with different fluorophores is established or broken. Therefore, it provides access to the characterization of a variety of cleavage and ligation reactions in biochem. Confocal fluorescence coincidence anal. is a very sensitive and ultrafast technique with readout times of 100 ms and below. This feature is demonstrated by means of a homogeneous assay for restriction endonuclease EcoRI. The presented achievements break ground for throughput rates as high as 106 samples per day with using only small amts. of sample substance and therefore constitute a solid base for screening applications in drug discovery and evolutionary biotechnol.
- 27Li, Y.; Gu, N. Thermodynamics of Charged Nanoparticle Adsorption on Charge-Neutral Membranes: A Simulation Study. J. Phys. Chem. B 2010, 114 (8), 2749– 2754, DOI: 10.1021/jp904550b27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhvVKitbg%253D&md5=cca79491b6f97e60da240c5885a71d63Thermodynamics of Charged Nanoparticle Adsorption on Charge-Neutral Membranes: A Simulation StudyLi, Yang; Gu, NingJournal of Physical Chemistry B (2010), 114 (8), 2749-2754CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)The interactions between charged nanoparticles (NPs) and charge-neutral phospholipid membranes are investigated by coarse-grained mol. dynamics simulations. Three kinds of nanoparticles are modeled with different surface charge densities: the uncharged one, the pos. charged one, and the neg. charged one. We find that the electrostatic attraction improves the adhesion of a charged nanoparticle to the membrane. With the increase of electrostatic energy, a charged NP can be almost fully wrapped by the membrane. In addn., analyses of structural variations suggest that the adhesion of a charged NP induces a local transition in fluid bilayers. Some thermodn. quantities such as free energy, entropy, and enthalpy are also obtained to explain the process of NPs binding. Furthermore, the bending energy of wrapping of NPs against the electrostatic potential energy is also discussed based on the Helfrich theory, indicating that the driving force of the wrap originates from the gain in electrostatic energy at the cost of the elastic energy of biomembranes. Our observations shed light on the origin of expts. of the wrap as well as the mechanism of structural transitions of membranes due to the electrostatic binding.
- 28Wang, B.; Zhang, L.; Bae, S. C.; Granick, S. Nanoparticle-Induced Surface Reconstruction of Phospholipid Membranes. Proc. Natl. Acad. Sci. U. S. A. 2008, 105 (47), 18171– 18175, DOI: 10.1073/pnas.080729610528https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhsVOmsb%252FP&md5=1b3d6555f4aea996fc460ede6c837c3bNanoparticle-induced surface reconstruction of phospholipid membranesWang, Bo; Zhang, Liangfang; Bae, Sung Chul; Granick, SteveProceedings of the National Academy of Sciences of the United States of America (2008), 105 (47), 18171-18175, S18171/1-S18171/5CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)The nonspecific adsorption of charged nanoparticles onto single-component phospholipid bilayers bearing phosphocholine headgroups is shown, from fluorescence and calorimetry expts., to cause surface reconstruction at the points where nanoparticles adsorb. Nanoparticles of neg. charge induce local gelation in otherwise fluid bilayers; nanoparticles of pos. charge induce otherwise gelled membranes to fluidize locally. Through this mechanism, the phase state deviates from the nominal phase transition temp. by tens of degrees. This work generalizes the notions of environmentally induced surface reconstruction, prominent in metals and semiconductors. Bearing in mind that chem. compn. in these single-component lipid bilayers is the same everywhere, this offers a mechanism to generate patchy functional properties in phospholipid membranes.
- 29Ruf, W. FXa Takes Center Stage in Vascular Inflammation. Blood 2014, 123 (11), 1630– 1631, DOI: 10.1182/blood-2014-02-553081There is no corresponding record for this reference.
- 30Cirino, G.; Cicala, C.; Bucci, M.; Sorrentino, L.; Ambrosini, G.; DeDominicis, G.; Altieri, D. C. Factor Xa as an Interface between Coagulation and Inflammation. Molecular Mimicry of Factor Xa Association with Effector Cell Protease Receptor-1 Induces Acute Inflammation in Vivo. J. Clin. Invest. 1997, 99 (10), 2446– 2451, DOI: 10.1172/JCI119428There is no corresponding record for this reference.
- 31Brook, R. D.; Franklin, B.; Cascio, W.; Hong, Y.; Howard, G.; Lipsett, M.; Luepker, R.; Mittleman, M.; Samet, J.; Smith, S. C. Air Pollution and Cardiovascular Disease: A Statement for Healthcare Professionals From the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation 2004, 109 (21), 2655– 2671, DOI: 10.1161/01.CIR.0000128587.30041.C8There is no corresponding record for this reference.
- 32Wang, F.; Yu, L.; Monopoli, M. P.; Sandin, P.; Mahon, E.; Salvati, A.; Dawson, K. A. The Biomolecular Corona Is Retained during Nanoparticle Uptake and Protects the Cells from the Damage Induced by Cationic Nanoparticles until Degraded in the Lysosomes. Nanomedicine 2013, 9 (8), 1159– 1168, DOI: 10.1016/j.nano.2013.04.01032https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtFSmtLnJ&md5=226fb91b5b40f2306ff904035e02a095The biomolecular corona is retained during nanoparticle uptake and protects the cells from the damage induced by cationic nanoparticles until degraded in the lysosomesWang, Fengjuan; Yu, Lu; Monopoli, Marco P.; Sandin, Peter; Mahon, Eugene; Salvati, Anna; Dawson, Kenneth A.Nanomedicine (New York, NY, United States) (2013), 9 (8), 1159-1168CODEN: NANOBF; ISSN:1549-9634. (Elsevier)Nanoparticles have unique capacities of interacting with the cellular machinery and entering cells. To be able to exploit this potential, it is essential to understand what controls the interactions at the interface between nanoparticles and cells: it is now established that nanoparticles in biol. media are covered by proteins and other biomols. forming a "corona" on the nanoparticle surface, which confers a new identity to the nanoparticles. By labeling the proteins of the serum, using pos.-charged polystyrene, we now show that this adsorbed layer is strong enough to be retained on the nanoparticles as they enter cells and is trafficked to the lysosomes on the nanoparticles. There, the corona is degraded and this is followed by lysosomal damage, leading to cytosolic release of lysosomal content, and ultimately apoptosis. Thus the corona protects the cells from the damage induced by the bare nanoparticle surface until enzymically cleared in the lysosomes. This study investigates the effects of protein corona that normally forms on the surface of nanoparticles during in vivo use, describing the steps of intracellular processing of such particles, to enhance our understanding of how these particles interact with the cellular machinery.
- 33Jimeno-Romero, A.; Oron, M.; Cajaraville, M. P.; Soto, M.; Marigómez, I. Nanoparticle Size and Combined Toxicity of TiO2 and DSLS (Surfactant) Contribute to Lysosomal Responses in Digestive Cells of Mussels Exposed to TiO2 Nanoparticles. Nanotoxicology 2016, 10 (8), 1168– 1176, DOI: 10.1080/17435390.2016.1196250There is no corresponding record for this reference.
- 34Zhu, Y.; Eaton, J. W.; Li, C. Titanium Dioxide (TiO2) Nanoparticles Preferentially Induce Cell Death in Transformed Cells in a Bak/Bax-Independent Fashion. PLoS One 2012, 7 (11), e50607, DOI: 10.1371/journal.pone.0050607There is no corresponding record for this reference.
- 35Anguissola, S.; Garry, D.; Salvati, A.; O’Brien, P. J.; Dawson, K. A. High Content Analysis Provides Mechanistic Insights on the Pathways of Toxicity Induced by Amine-Modified Polystyrene Nanoparticles. PLoS One 2014, 9 (9), e108025, DOI: 10.1371/journal.pone.010802535https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhslSisr7J&md5=0f6e608a4c656c70b471a69098d4a311High content analysis provides mechanistic insights on the pathways of toxicity induced by amine-modified polystyrene nanoparticlesAnguissola, Sergio; Garry, David; Salvati, Anna; O'Brien, Peter J.; Dawson, Kenneth A.PLoS One (2014), 9 (9), e108025/1-e108025/16, 16 pp.CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)The fast-paced development of nanotechnol. needs the support of effective safety testing. We have developed a screening platform measuring simultaneously several cellular parameters for exposure to various concns. of nanoparticles (NPs). Cell lines representative of different organ cell types, including lung, endothelium, liver, kidney, macrophages, glia, and neuronal cells were exposed to 50 nm amine-modified polystyrene (PS-NH2) NPs previously reported to induce apoptosis and to 50 nm sulfonated and carboxyl-modified polystyrene NPs that were reported to be silent. All cell lines apart from Raw 264.7 executed apoptosis in response to PS-NH2 NPs, showing specific sequences of EC50 thresholds; lysosomal acidification was the most sensitive parameter. Loss of mitochondrial membrane potential and plasma membrane integrity measured by High Content Anal. resulted comparably sensitive to the equiv. OECD-recommended assays, allowing increased output. Anal. of the acidic compartments revealed good cerrelation between size/fluorescence intensity and dose of PS-NH2 NPs applied; moreover steatosis and phospholipidosis were obsd., consistent with the lysosomal alterations revealed by Lysotracker green; similar responses were obsd. when comparing astrocytoma cells with primary astrocytes. We have established a platform providing mechanistic insights on the response to exposure to nanoparticles. Such platform holds great potential for in vitro screening of nanomaterials in highthroughput format.
- 36Stern, S. T.; Adiseshaiah, P. P.; Crist, R. M. Autophagy and Lysosomal Dysfunction as Emerging Mechanisms of Nanomaterial Toxicity. Part. Fibre Toxicol. 2012, 9, 20, DOI: 10.1186/1743-8977-9-2036https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFCjurY%253D&md5=11cdb360401c2abf5759ced2cc60e352Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicityStern, Stephan T.; Adiseshaiah, Pavan P.; Crist, Rachael M.Particle and Fibre Toxicology (2012), 9 (), 20CODEN: PFTABQ; ISSN:1743-8977. (BioMed Central Ltd.)The study of the potential risks assocd. with the manuf., use, and disposal of nanoscale materials, and their mechanisms of toxicity, is important for the continued advancement of nanotechnol. Currently, the most widely accepted paradigms of nanomaterial toxicity are oxidative stress and inflammation, but the underlying mechanisms are poorly defined. This review will highlight the significance of autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Most endocytic routes of nanomaterial cell uptake converge upon the lysosome, making the lysosomal compartment the most common intracellular site of nanoparticle sequestration and degrdn. In addn. to the endo-lysosomal pathway, recent evidence suggests that some nanomaterials can also induce autophagy. Among the many physiol. functions, the lysosome, by way of the autophagy (macroautophagy) pathway, degrades intracellular pathogens, and damaged organelles and proteins. Thus, autophagy induction by nanoparticles may be an attempt to degrade what is perceived by the cell as foreign or aberrant. While the autophagy and endo-lysosomal pathways have the potential to influence the disposition of nanomaterials, there is also a growing body of literature suggesting that biopersistent nanomaterials can, in turn, neg. impact these pathways. Indeed, there is ample evidence that biopersistent nanomaterials can cause autophagy and lysosomal dysfunctions resulting in toxicol. consequences.
- 37Umek, P.; Korošec, R. C.; Jančar, B.; Dominko, R.; Arčon, D. The Influence of the Reaction Temperature on the Morphology of Sodium Titanate 1D Nanostructures and Their Thermal Stability. J. Nanosci. Nanotechnol. 2007, 7 (10), 3502– 3508, DOI: 10.1166/jnn.2007.838There is no corresponding record for this reference.
- 38Akashi, K.; Miyata, H.; Itoh, H.; Kinosita, K. Preparation of Giant Liposomes in Physiological Conditions and Their Characterization under an Optical Microscope. Biophys. J. 1996, 71 (6), 3242– 3250, DOI: 10.1016/S0006-3495(96)79517-6There is no corresponding record for this reference.
- 39Cox, J.; Hein, M. Y.; Luber, C. A.; Paron, I.; Nagaraj, N.; Mann, M. Accurate Proteome-Wide Label-Free Quantification by Delayed Normalization and Maximal Peptide Ratio Extraction, Termed MaxLFQ. Mol. Cell. Proteomics 2014, 13 (9), 2513– 2526, DOI: 10.1074/mcp.M113.03159139https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsVynurrI&md5=f3f1c7dc8fbf729c568446968b89f37cAccurate Proteome-wide Label-free Quantification by Delayed Normalization and Maximal Peptide Ratio Extraction, Termed MaxLFQCox, Juergen; Hein, Marco Y.; Luber, Christian A.; Paron, Igor; Nagaraj, Nagarjuna; Mann, MatthiasMolecular & Cellular Proteomics (2014), 13 (9), 2513-2526CODEN: MCPOBS; ISSN:1535-9484. (American Society for Biochemistry and Molecular Biology)Protein quantification without isotopic labels has been a long-standing interest in the proteomics field. However, accurate and robust proteome-wide quantification with label-free approaches remains a challenge. We developed a new intensity detn. and normalization procedure called MaxLFQ that is fully compatible with any peptide or protein sepn. prior to LC-MS anal. Protein abundance profiles are assembled using the max. possible information from MS signals, given that the presence of quantifiable peptides varies from sample to sample. For a benchmark dataset with two proteomes mixed at known ratios, we accurately detected the mixing ratio over the entire protein expression range, with greater precision for abundant proteins. The significance of individual label-free quantifications was obtained via a t test approach. For a second benchmark dataset, we accurately quantify fold changes over several orders of magnitude, a task that is challenging with label-based methods. MaxLFQ is a generic label-free quantification technol. that is readily applicable to many biol. questions; it is compatible with std. statistical anal. workflows, and it has been validated in many and diverse biol. projects. Our algorithms can handle very large expts. of 500+ samples in a manageable computing time. It is implemented in the freely available MaxQuant computational proteomics platform and works completely seamlessly at the click of a button.
Supporting Information
Supporting Information
Supporting Information is available free of charge via the Internet at The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.nanolett.8b02291.
Motivation, material, equipment, preparation of the samples, measurements of zeta-potential, fluorescence microspectrosopy (FMS), dynamic light scattering (DLS), experiments based on fluorescence fluctuations, confocal and STED fluorescence imaging of LUV and NP, fluorescence spectroscopy of NP and LUV, STED imaging of LA-4 cells and NP, lactate dehidrogenase (LDH) assay, cell viability test (hoechst and propidium iodide), determination of plasma membrane fraction used in wrapping of TiO2 nanotubes, proteomic analysis of lipid-protein corona on TiO2 nanotubes, additional comments, references (PDF)
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