Defining the Surface Oxygen Threshold That Switches the Interaction Mode of Graphene Oxide with BacteriaClick to copy article linkArticle link copied!
- Zhiling Guo*Zhiling Guo*Email: [email protected]School of Geography, Earth and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United KingdomMore by Zhiling Guo
- Peng Zhang*Peng Zhang*Email: [email protected]School of Geography, Earth and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United KingdomDepartment of Environmental Science and Engineering, University of Science and Technology of China, Hefei 230026, ChinaMore by Peng Zhang
- Changjian Xie*Changjian Xie*Email: [email protected]School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255000, Shandong, ChinaMore by Changjian Xie
- Evangelos VoyiatzisEvangelos VoyiatzisNanoinformatics Department, NovaMechanics Ltd., Nicosia, 1065, CyprusMore by Evangelos Voyiatzis
- Klaus FaserlKlaus FaserlInstitute of Medical Biochemistry, Medical University of Innsbruck, 6020 Innsbruck, AustriaMore by Klaus Faserl
- Andrew J. ChetwyndAndrew J. ChetwyndSchool of Geography, Earth and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United KingdomMore by Andrew J. Chetwynd
- Fazel Abdolahpur MonikhFazel Abdolahpur MonikhDepartment of Environmental & Biological Sciences, University of Eastern Finland, P.O. Box 111, Joensuu, FI-80101, FinlandMore by Fazel Abdolahpur Monikh
- Georgia MelagrakiGeorgia MelagrakiNanoinformatics Department, NovaMechanics Ltd., Nicosia, 1065, CyprusMore by Georgia Melagraki
- Zhiyong ZhangZhiyong ZhangKey Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, ChinaSchool of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing 100049, ChinaMore by Zhiyong Zhang
- Willie J. G. M. PeijnenburgWillie J. G. M. PeijnenburgInstitute of Environmental Sciences (CML), Leiden University, Einsteinweg 2, 2333 CC Leiden, The NetherlandsNational Institute of Public Health and the Environment (RIVM), Center for Safety of Substances and Products, 3720 BA Bilthoven, The NetherlandsMore by Willie J. G. M. Peijnenburg
- Antreas AfantitisAntreas AfantitisNanoinformatics Department, NovaMechanics Ltd., Nicosia, 1065, CyprusMore by Antreas Afantitis
- Chunying ChenChunying ChenCAS Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, ChinaResearch Unit of Nanoscience and Technology, Chinese Academy of Medical Sciences, Beijing 100039, ChinaGBA National Institute for Nanotechnology Innovation, Guangdong 510700, ChinaResearch Unit of Nanoscience and Technology, Chinese Academy of Medical Sciences, Beijing 100021, ChinaMore by Chunying Chen
- Iseult LynchIseult LynchSchool of Geography, Earth and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United KingdomMore by Iseult Lynch
Abstract
As antimicrobials, graphene materials (GMs) may have advantages over traditional antibiotics due to their physical mechanisms of action which ensure less chance of development of microbial resistance. However, the fundamental question as to whether the antibacterial mechanism of GMs originates from parallel interaction or perpendicular interaction, or from a combination of these, remains poorly understood. Here, we show both experimentally and theoretically that GMs with high surface oxygen content (SOC) predominantly attach in parallel to the bacterial cell surface when in the suspension phase. The interaction mode shifts to perpendicular interaction when the SOC reaches a threshold of ∼0.3 (the atomic percent of O in the total atoms). Such distinct interaction modes are highly related to the rigidity of GMs. Graphene oxide (GO) with high SOC is very flexible and thus can wrap bacteria while reduced GO (rGO) with lower SOC has higher rigidity and tends to contact bacteria with their edges. Neither mode necessarily kills bacteria. Rather, bactericidal activity depends on the interaction of GMs with surrounding biomolecules. These findings suggest that variation of SOC of GMs is a key factor driving the interaction mode with bacteria, thus helping to understand the different possible physical mechanisms leading to their antibacterial activity.
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License Summary*
You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:
Creative Commons (CC): This is a Creative Commons license.
Attribution (BY): Credit must be given to the creator.
*Disclaimer
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License Summary*
You are free to share(copy and redistribute) this article in any medium or format and to adapt(remix, transform, and build upon) the material for any purpose, even commercially within the parameters below:
Creative Commons (CC): This is a Creative Commons license.
Attribution (BY): Credit must be given to the creator.
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Introduction
Results and Discussion
Antibacterial Activity of GMs Controlled by an SOC Threshold
Intrinsic Oxidative Potential of GMs Is Not the Main Factor Leading to Their Distinct Antibacterial Activity
SOC-Dependent Physical Disruption of Bacterial Membrane Is the Main Contributor to the Antibacterial Activity
Transition of Parallel to Perpendicular Interaction Mode Controlled by an SOC Threshold
SOC-Dependent Protein Corona Formation on GMs Changes Their Antibacterial Activity
Conclusions
Experimental Methods
Antibacterial Activity of GMs
Examination of Membrane Integrity
Measurement of ROS in Bacterial Cells
Measurement of O2•– in GM Suspensions
GSH Oxidation Assay
Physical Interaction of GMs with Liposomes
SEM Images
Thickness Analysis by AFM
Protein Corona Composition Analyzed by Proteomic Analysis
Molecular Dynamics (MD) Simulation
Statistical Analysis
Data Availability
The data supporting the findings of this study are available within the paper and its Supporting Information and in the PRIDE repository with the identifier PXD027909. Source data are provided with this paper.
Supporting Information
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.2c10961.
Details materials and methods, survey of the SOC literature of GMs on the antibacterial effects, the characterization of GMs, the antibacterial effects and the potential antibacterial mechanism of GMs, liposome leakage, and MD simulation studies (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 financially supported by the National Natural Science Foundation of China (Grant No. 12105163, 11405183, 21507153, 11275215, and 11275218), Natural Science Foundation of Shandong Province (Grant No. ZR2020QD133), Ministry of Science and Technology of China (Grant No. 2013CB932703), The Engineering and Physical Sciences Research Council Impact Acceleration Accounts Developing Leaders (Grant No. 1001634) and EU H2020 project NanoSolveIT (Grant Agreement 814572), RiskGone (Grant Agreement 814425), and NanoCommons (Grant Agreement 731032). Funding support from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement (754340) and Royal Society International Exchange Programs (1853690 and 2122860) are also acknowledged.
References
This article references 30 other publications.
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- 4Zhao, J.; Deng, B.; Lv, M.; Li, J.; Zhang, Y.; Jiang, H.; Peng, C.; Li, J.; Shi, J.; Huang, Q. Graphene Oxide-Based Antibacterial Cotton Fabrics. Adv. Healthc. Mater. 2013, 2 (9), 1259– 1266, DOI: 10.1002/adhm.201200437Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVSlsL3K&md5=b59829e8096c3759d9c1762abf530272Graphene Oxide-Based Antibacterial Cotton FabricsZhao, Jinming; Deng, Bo; Lv, Min; Li, Jingye; Zhang, Yujie; Jiang, Haiqing; Peng, Cheng; Li, Jiang; Shi, Jiye; Huang, Qing; Fan, ChunhaiAdvanced Healthcare Materials (2013), 2 (9), 1259-1266CODEN: AHMDBJ; ISSN:2192-2640. (Wiley-VCH Verlag GmbH & Co. KGaA)Graphene oxide (GO) is an excellent bacteria-killing nanomaterial. In this work, macroscopic applications of this promising nanomaterial by fixing GO sheets onto cotton fabrics, which possess strong antibacterial property and great laundering durability, are reported. The GO-based antibacterial cotton fabrics are prepd. in 3 ways: direct adsorption, radiation-induced crosslinking, and chem. crosslinking. Antibacterial tests show that all these GO-contg. fabrics possess strong antibacterial property and could inactivate 98% of bacteria. Most significantly, these fabrics can still kill >90% bacteria even after being washed for 100 times. Also importantly, animal tests show that GO-modified cotton fabrics cause no irritation to rabbit skin. Hence, it is believed that these flexible, foldable, and re-usable GO-based antibacterial cotton fabrics have high promise as a type of new nano-engineered antibacterial materials for a wide range of applications.
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- 8Fadeel, B.; Bussy, C.; Merino, S.; Vázquez, E.; Flahaut, E.; Mouchet, F.; Evariste, L.; Gauthier, L.; Koivisto, A. J.; Vogel, U. Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment. ACS Nano 2018, 12 (11), 10582– 10620, DOI: 10.1021/acsnano.8b04758Google Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVyju7nN&md5=f276495b7b3b777acedf279460618b25Safety Assessment of Graphene-Based Materials: Focus on Human Health and the EnvironmentFadeel, Bengt; Bussy, Cyrill; Merino, Sonia; Vazquez, Ester; Flahaut, Emmanuel; Mouchet, Florence; Evariste, Lauris; Gauthier, Laury; Koivisto, Antti J.; Vogel, Ulla; Martin, Cristina; Delogu, Lucia G.; Buerki-Thurnherr, Tina; Wick, Peter; Beloin-Saint-Pierre, Didier; Hischier, Roland; Pelin, Marco; Candotto Carniel, Fabio; Tretiach, Mauro; Cesca, Fabrizia; Benfenati, Fabio; Scaini, Denis; Ballerini, Laura; Kostarelos, Kostas; Prato, Maurizio; Bianco, AlbertoACS Nano (2018), 12 (11), 10582-10620CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. Graphene and its derivs. are heralded as "miracle" materials with manifold applications in different sectors of society from electronics to energy storage to medicine. The increasing exploitation of graphene-based materials (GBMs) necessitates a comprehensive evaluation of the potential impact of these materials on human health and the environment. Here, we discuss synthesis and characterization of GBMs as well as human and environmental hazard assessment of GBMs using in vitro and in vivo model systems with the aim to understand the properties that underlie the biol. effects of these materials; not all GBMs are alike, and it is essential that we disentangle the structure-activity relationships for this class of materials.
- 9Hegab, H. M.; ElMekawy, A.; Zou, L.; Mulcahy, D.; Saint, C. P.; Ginic-Markovic, M. The Controversial Antibacterial Activity of Graphene-Based Materials. Carbon 2016, 105, 362– 376, DOI: 10.1016/j.carbon.2016.04.046Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xntlyntbc%253D&md5=d673e60450126e3f4ec9d9d2e0f9b74fThe controversial antibacterial activity of graphene-based materialsHegab, Hanaa M.; El Mekawy, Ahmed; Zou, Linda; Mulcahy, Dennis; Saint, Christopher P.; Ginic-Markovic, MilenaCarbon (2016), 105 (), 362-376CODEN: CRBNAH; ISSN:0008-6223. (Elsevier Ltd.)A review. Graphene (Gr)-based materials are a promising nanomaterial for the development of antibacterial surfaces owing to their biocidal activity. However, the effect of the physicochem. features of these materials on their antibacterial activity has yet to be clarified. Gr-based nanomaterials can interact with cellular components, e.g. membranes, proteins and DNA, and initiate a sequence of nanomaterials/bacterial interactions that rely on colloidal energies and active bio-physicochem. interfaces. Analyzing these different interfaces permits the development of anticipated relations between phys./chem. structure and bactericidal activity depending on Gr-based nanomaterial features such as shape, size, hydrophilicity, roughness and functionality. Realizing how nanomaterials are interacting with bacterial cell membranes is correlated to how they affect bactericidal activity and is thus crit. for obtaining benign applications. This review anal. discusses specific Gr-based material features related to bacterial interactions, with special focus on the different modes of interaction between Gr-based materials and cell membranes, nucleic acids and lipid bilayers.
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- 11Tu, Y.; Lv, M.; Xiu, P.; Huynh, T.; Zhang, M.; Castelli, M.; Liu, Z.; Huang, Q.; Fan, C.; Fang, H. Destructive Extraction of Phospholipids from Escherichia Coli Membranes by Graphene Nanosheets. Nat. Nanotechnol. 2013, 8 (8), 594– 601, DOI: 10.1038/nnano.2013.125Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVKhtL7O&md5=7f60957a5cc3b8008520ab5aeb9858adDestructive extraction of phospholipids from Escherichia coli membranes by graphene nanosheetsTu, Yusong; Lv, Min; Xiu, Peng; Huynh, Tien; Zhang, Meng; Castelli, Matteo; Liu, Zengrong; Huang, Qing; Fan, Chunhai; Fang, Haiping; Zhou, RuhongNature Nanotechnology (2013), 8 (8), 594-601CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)Understanding how nanomaterials interact with cell membranes is related to how they cause cytotoxicity and is therefore crit. for designing safer biomedical applications. Recently, graphene (a two-dimensional nanomaterial) was shown to have antibacterial activity on Escherichia coli, but its underlying mol. mechanisms remain unknown. Here we show exptl. and theor. that pristine graphene and graphene oxide nanosheets can induce the degrdn. of the inner and outer cell membranes of Escherichia coli, and reduce their viability. TEM shows three rough stages, and mol. dynamics simulations reveal the at. details of the process. Graphene nanosheets can penetrate into and ext. large amts. of phospholipids from the cell membranes because of the strong dispersion interactions between graphene and lipid mols. This destructive extn. offers a novel mechanism for the mol. basis of graphene's cytotoxicity and antibacterial activity.
- 12Li, Y.; Yuan, H.; von Dem Bussche, A.; Creighton, M.; Hurt, R. H.; Kane, A. B.; Gao, H. Graphene Microsheets Enter Cells Through Spontaneous Membrane Penetration at Edge Asperities and Corner Sites. Proc. Natl. Acad. Sci. U.S.A. 2013, 110 (30), 12295– 12300, DOI: 10.1073/pnas.1222276110Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1emu7vL&md5=6857eb72d9a20857dfd8b5f6f6c491a7Graphene microsheets enter cells through spontaneous membrane penetration at edge asperities and corner sitesLi, Yinfeng; Yuan, Hongyan; von dem Bussche, Annette; Creighton, Megan; Hurt, Robert H.; Kane, Agnes B.; Gao, HuajianProceedings of the National Academy of Sciences of the United States of America (2013), 110 (30), 12295-12300,S12295/1-S12295/11CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Understanding and controlling the interaction of graphene-based materials with cell membranes is key to the development of graphene-enabled biomedical technologies and to the management of graphene health and safety issues. Very little is known about the fundamental behavior of cell membranes exposed to ultrathin 2D synthetic materials. Here we investigate the interactions of graphene and few-layer graphene (FLG) microsheets with three cell types and with model lipid bilayers by combining coarse-grained mol. dynamics (MD), all-atom MD, anal. modeling, confocal fluorescence imaging, and electron microscopic imaging. The imaging expts. show edge-first uptake and complete internalization for a range of FLG samples of 0.5- to 10-μm lateral dimension. In contrast, the simulations show large energy barriers relative to kBT for membrane penetration by model graphene or FLG microsheets of similar size. More detailed simulations resolve this paradox by showing that entry is initiated at corners or asperities that are abundant along the irregular edges of fabricated graphene materials. Local piercing by these sharp protrusions initiates membrane propagation along the extended graphene edge and thus avoids the high energy barrier calcd. in simple idealized MD simulations. We propose that this mechanism allows cellular uptake of even large multilayer sheets of micrometer-scale lateral dimension, which is consistent with our multimodal bioimaging results for primary human keratinocytes, human lung epithelial cells, and murine macrophages.
- 13Lu, X.; Feng, X.; Werber, J. R.; Chu, C.; Zucker, I.; Kim, J.-H.; Osuji, C. O.; Elimelech, M. Enhanced Antibacterial Activity Through the Controlled Alignment of Graphene Oxide Nanosheets. Proc. Natl. Acad. Sci. U.S.A. 2017, 114 (46), E9793– E9801, DOI: 10.1073/pnas.1710996114Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslagtbvJ&md5=31b1dc68115ba48371cb8836d9f54b97Enhanced antibacterial activity through the controlled alignment of graphene oxide nanosheetsLu, Xinglin; Feng, Xunda; Werber, Jay R.; Chu, Chiheng; Zucker, Ines; Kim, Jae-Hong; Osuji, Chinedum O.; Elimelech, MenachemProceedings of the National Academy of Sciences of the United States of America (2017), 114 (46), E9793-E9801CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)The cytotoxicity of 2D graphene-based nanomaterials (GBNs) is highly important for engineered applications and environmental health. However, the isotropic orientation of GBNs, most notably graphene oxide (GO), in previous exptl. studies obscured the interpretation of cytotoxic contributions of nanosheet edges. Here, we investigate the orientation-dependent interaction of GBNs with bacteria using GO composite films. To produce the films, GO nanosheets are aligned in a magnetic field, immobilized by crosslinking of the surrounding matrix, and exposed on the surface through oxidative etching. Characterization by small-angle X-ray scattering and at. force microscopy confirms that GO nanosheets align progressively well with increasing magnetic field strength and that the alignment is effectively preserved by crosslinking. When contacted with the model bacterium Escherichia coli, GO nanosheets with vertical orientation exhibit enhanced antibacterial activity compared with random and horizontal orientations. Further characterization is performed to explain the enhanced antibacterial activity of the film with vertically aligned GO. Using phospholipid vesicles as a model system, we observe that GO nanosheets induce phys. disruption of the lipid bilayer. Addnl., we find substantial GO-induced oxidn. of glutathione, a model intracellular antioxidant, paired with limited generation of reactive oxygen species, suggesting that oxidn. occurs through a direct electron-transfer mechanism. These phys. and chem. mechanisms both require nanosheet penetration of the cell membrane, suggesting that the enhanced antibacterial activity of the film with vertically aligned GO stems from an increased d. of edges with a preferential orientation for membrane disruption. The importance of nanosheet penetration for cytotoxicity has direct implications for the design of engineering surfaces using GBNs.
- 14Mejías Carpio, I. E.; Santos, C. M.; Wei, X.; Rodrigues, D. F. Toxicity of a Polymer–Graphene Oxide Composite Against Bacterial Planktonic Cells, Biofilms, and Mammalian Cells. Nanoscale 2012, 4 (15), 4746– 4756, DOI: 10.1039/c2nr30774jGoogle Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVSqt7rK&md5=37a4406506d358ada320fce50c410c9cToxicity of a polymer-graphene oxide composite against bacterial planktonic cells, biofilms, and mammalian cellsMejias Carpio, Isis E.; Santos, Catherine M.; Wei, Xin; Rodrigues, Debora F.Nanoscale (2012), 4 (15), 4746-4756CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)It is crit. to develop highly effective antimicrobial agents that are not harmful to humans and do not present adverse effects on the environment. Although antimicrobial studies of graphene-based nanomaterials are still quite limited, some researchers have paid particular attention to such nanocomposites as promising candidates for the next generation of antimicrobial agents. The polyvinyl-N-carbazole (PVK)-graphene oxide (GO) nanocomposite (PVK-GO), which contains only 3 wt% of GO well-dispersed in a 97 wt% PVK matrix, presents excellent antibacterial properties without significant cytotoxicity to mammalian cells. The high polymer content in this nanocomposite makes future large-scale material manufg. possible in a high-yield process of adiabatic bulk polymn. In this study, the toxicity of PVK-GO was assessed with planktonic microbial cells, biofilms, and NIH 3T3 fibroblast cells. The antibacterial effects were evaluated against 2 Gram-neg. bacteria: Escherichia coli and Cupriavidus metallidurans; and 2 Gram-pos. bacteria: Bacillus subtilis and Rhodococcus opacus. The results show that the PVK-GO nanocomposite presents higher antimicrobial effects than the pristine GO. The effectiveness of the PVK-GO in soln. was demonstrated as the nanocomposite "encapsulated" the bacterial cells, which led to reduced microbial metabolic activity and cell death. The fact that the PVK-GO did not present significant cytotoxicity to fibroblast cells offers a great opportunity for potential applications in important biomedical and industrial fields.
- 15Mangadlao, J. D.; Santos, C. M.; Felipe, M. J. L.; de Leon, A. C. C.; Rodrigues, D. F.; Advincula, R. C. On the Antibacterial Mechanism of Graphene Oxide (GO) Langmuir–Blodgett Films. Chem. Commun. 2015, 51 (14), 2886– 2889, DOI: 10.1039/C4CC07836EGoogle Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitFegtr3E&md5=145624f5f2cdb4f7da6cf4949c2374c5On the antibacterial mechanism of graphene oxide (GO) Langmuir-Blodgett filmsMangadlao, J. D.; Santos, C. M.; Felipe, M. J. L.; de Leon, A. C. C.; Rodrigues, D. F.; Advincula, R. C.Chemical Communications (Cambridge, United Kingdom) (2015), 51 (14), 2886-2889CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)The Langmuir-Blodgett (LB) technique was used to immobilize flat graphene oxide (GO) sheets on a PET substrate to ascertain as to whether the edges of GO play an integral part in its antimicrobial mechanism. The obsd. antibacterial activity suggests that contact with the edges is not a fundamental part of the mechanism.
- 16Zucker, I.; Werber, J. R.; Fishman, Z. S.; Hashmi, S. M.; Gabinet, U. R.; Lu, X.; Osuji, C. O.; Pfefferle, L. D.; Elimelech, M. Loss of Phospholipid Membrane Integrity Induced by Two-Dimensional Nanomaterials. Environ. Sci. Technol. Lett. 2017, 4 (10), 404– 409, DOI: 10.1021/acs.estlett.7b00358Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsVKmtb7F&md5=7e5c90f397af8b520af0b381359a6bf5Loss of Phospholipid Membrane Integrity Induced by Two-Dimensional NanomaterialsZucker, Ines; Werber, Jay R.; Fishman, Zachary S.; Hashmi, Sara M.; Gabinet, Uri R.; Lu, Xinglin; Osuji, Chinedum O.; Pfefferle, Lisa D.; Elimelech, MenachemEnvironmental Science & Technology Letters (2017), 4 (10), 404-409CODEN: ESTLCU; ISSN:2328-8930. (American Chemical Society)The interaction of two-dimensional (2D) nanomaterials with biol. membranes has important implications for ecotoxicity and human health. In this study, the authors use a dye-leakage assay to quant. assess the disruption of a model phospholipid bilayer membrane (i.e., lipid vesicles) by five emerging 2D nanomaterials: graphene oxide (GO), reduced graphene oxide (rGO), molybdenum disulfide (MoS2), copper oxide (CuO), and iron oxide (α-Fe2O3). Leakage of dye from the vesicle inner soln., which indicates loss of membrane integrity, was obsd. for GO, rGO, and MoS2 nanosheets but not for CuO and α-Fe2O3, implying that 2D morphol. by itself is not sufficient to cause loss of membrane integrity. Mixing GO and rGO with lipid vesicles induced aggregation, whereas enhanced stability (dispersion) was obsd. with MoS2 nanosheets, suggesting different aggregation mechanisms for the 2D nanomaterials upon interaction with lipid bilayers. No loss of membrane integrity was obsd. under strong oxidative conditions, indicating that nanosheet-driven membrane disruption stemmed from a phys. mechanism rather than chem. oxidn. For GO, the most disruptive nanomaterial, the authors show that the extent of membrane integrity loss was dependent on total surface area, not edge length, which is consistent with a lipid-extn. mechanism and inconsistent with a piercing mechanism.
- 17Xie, C.; Zhang, P.; Guo, Z.; Li, X.; Pang, Q.; Zheng, K.; He, X.; Ma, Y.; Zhang, Z.; Lynch, I. Elucidating the Origin of the Surface Functionalization-Dependent Bacterial Toxicity of Graphene Nanomaterials: Oxidative Damage, Physical Disruption, and Cell Autolysis. Sci. Total Environ. 2020, 747, 141546, DOI: 10.1016/j.scitotenv.2020.141546Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsFykurvJ&md5=8cb7b85b78ed9ae62470baf21c95118dElucidating the origin of the surface functionalization - dependent bacterial toxicity of graphene nanomaterials: Oxidative damage, physical disruption, and cell autolysisXie, Changjian; Zhang, Peng; Guo, Zhiling; Li, Xiaowei; Pang, Qiuxiang; Zheng, Kang; He, Xiao; Ma, Yuhui; Zhang, Zhiyong; Lynch, IseultScience of the Total Environment (2020), 747 (), 141546CODEN: STENDL; ISSN:0048-9697. (Elsevier B.V.)Previous studies have shown that the toxicity of graphene nanomaterials (GNMs) to bacteria are related to the surface functionalization, however, the involved mechanisms are not fully understood. The present study aims to explore the toxic mechanisms of differentially functionalized GNMs to bacteria from the aspects of phys. interaction, oxidative damage and cell autolysis. Three basic functionalization of GNMs including carboxylation (G-COOH), hydroxylation (G-OH) and amination (G-NH2) were studied. G-COOH (66% viability vs. CT group) and G-OH (54%) graphene showed higher toxicity to E. coli than G-NH2 (96%) within 3 h at a concn. of 50 mg/L. The three materials showed distinct phys. interaction modes with bacterial cells. G-COOH and G-OH contact with cell membrane via their sharp edges thus causing more damage than G-NH2 which covered the bacteria attaching along the basal plane. The three GNMs showed similar radical generation capacities, thus the direct generation of radicals is not the mechanism causing the toxicity. Instead, the GNMs can oxidize the cellular antioxidant glutathione (GSH) thereby causing oxidative damage. The oxidative capacity follows the order: G-COOH > G-OH > G-NH2, which correlated with the antibacterial activity. Cell autolysis, the degrdn. of cell wall component peptidoglycan, was found to be a new mechanism inducing the death of bacteria. G-COOH and G-OH caused more cell autolysis than G-NH2, which accounts partially for the different toxicity of the three GNMs. The findings provide significant insights into the mechanism of GNMs toxicity to bacteria for not only the risk assessment of GNMs but also the design of graphene based antibacterial materials.
- 18Hou, W.-C.; Lee, P.-L.; Chou, Y.-C.; Wang, Y.-S. Antibacterial Property of Graphene Oxide: the Role of Phototransformation. Environ. Sci. Nano 2017, 4 (3), 647– 657, DOI: 10.1039/C6EN00427JGoogle Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXltlCnsA%253D%253D&md5=44ef2d666618d6f26f135ad6bfc57423Antibacterial property of graphene oxide: the role of phototransformationHou, Wen-Che; Lee, Pei-Ling; Chou, Yu-Chieh; Wang, Yi-ShengEnvironmental Science: Nano (2017), 4 (3), 647-657CODEN: ESNNA4; ISSN:2051-8161. (Royal Society of Chemistry)Graphene-related materials are emerging with a wide range of potential applications. Their possible ecol. effect must be properly evaluated before their widespread use. This study examd. the antibacterial activity of graphene oxide (GO) before and after solar transformation under two reaction scenarios. GO was directly phototransformed under simulated sunlight or indirectly photolyzed by photochem. generated hydroxyl radical (̇ OH). The results indicate that compared to parent GO, directly phototransformed GO showed increased toxicity to bacteria, while the indirectly phototransformed GO became less toxic. The reduced bacterial toxicity of indirectly photolyzed GO correlated with its large decrease in total org. carbon (TOC) concn. after the indirect photoreaction. In contrast, the directly phototransformed GO caused greater membrane disruption and oxidative stress, which is consistent with its increased antibacterial activity. The oxidative stress was likely assocd. with the intrinsic oxidn. capability of the directly photolyzed GO. Given that direct photolysis of GO is expected to occur more rapidly in sunlit surface waters, as predicted in previous research, enhanced antibacterial activity of phototransformed GO will likely dominate the initial solar transformation of GO, while microbial toxicity will decrease in long term photolysis where GO is extensively decompd. bẏ OH-mediated photoreaction.
- 19Vecitis, C. D.; Zodrow, K. R.; Kang, S.; Elimelech, M. Electronic-Structure-Dependent Bacterial Cytotoxicity of Single-Walled Carbon Nanotubes. ACS Nano 2010, 4 (9), 5471– 5479, DOI: 10.1021/nn101558xGoogle Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtFSlsrjE&md5=8ed380e81d17ed28a7dd52e81f026625Electronic-Structure-Dependent Bacterial Cytotoxicity of Single-Walled Carbon NanotubesVecitis, Chad D.; Zodrow, Katherine R.; Kang, Seoktae; Elimelech, MenachemACS Nano (2010), 4 (9), 5471-5479CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Single-walled carbon nanotubes (SWNTs) have been previously obsd. to be strong antimicrobial agents, and SWNT coatings can significantly reduce biofilm formation. However, the SWNT antimicrobial mechanism is not fully understood. Previous studies on SWNT cytotoxicity have concluded that membrane stress (i.e., direct SWNT-bacteria contact resulting in membrane perturbation and the release of intracellular contents) was the primary cause of cell death. Gene expression studies have indicated oxidative stress may be active, as well. Here, it is demonstrated for the first time how SWNT electronic structure (i.e., metallic vs. semiconducting) is a key factor regulating SWNT antimicrobial activity. Expts. were performed with well-characterized SWNTs of similar length and diam. but varying fraction of metallic nanotubes. Loss of Escherichia coli viability was obsd. to increase with an increasing fraction of metallic SWNTs. Time-dependent cytotoxicity measurements indicated that in all cases the majority of the SWNT antimicrobial action occurs shortly after (<15 min) bacteria-SWNT contact. The SWNT toxicity mechanism was investigated by in vitro SWNT-mediated oxidn. of glutathione, a common intracellular thiol that serves as an antioxidant and redox state mediator. The extent of glutathione oxidn. was obsd. to increase with increasing fraction of metallic SWNTs, indicating an elevated role of oxidative stress. SEM images of E. coli in contact with the SWNTs demonstrated electronic structure-dependent morphol. changes consistent with cytotoxicity and glutathione oxidn. results. A three-step SWNT antimicrobial mechanism is proposed involving (i) initial SWNT-bacteria contact, (ii) perturbation of the cell membrane, and (ii) electronic structure-dependent bacterial oxidn.
- 20Barrios, A. C.; Wang, Y.; Gilbertson, L. M.; Perreault, F. Structure–Property–Toxicity Relationships of Graphene Oxide: Role of Surface Chemistry on the Mechanisms of Interaction with Bacteria. Environ. Sci. Technol. 2019, 53 (24), 14679– 14687, DOI: 10.1021/acs.est.9b05057Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitFWlsrzN&md5=93afc64dd4f61e486fdb6d03774bc942Structure-Property-Toxicity Relationships of Graphene Oxide: Role of Surface Chemistry on the Mechanisms of Interaction with BacteriaBarrios, Ana C.; Wang, Yan; Gilbertson, Leanne M.; Perreault, FrancoisEnvironmental Science & Technology (2019), 53 (24), 14679-14687CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)Graphene oxide (GO) is an antimicrobial with tunable surface chem. To identify the physicochem. determinants of GO's antimicrobial activity, we generated different modified Hummer's GO materials thermally annealed (at 200, 500, or 800 °C) to modify the surface oxygen groups. The plating assays show that as received GO (ARGO) and TGO200, TGO500 and TGO800 reduce E. coli viability by 50% (EC50) at 183, 143, 127 and 86 μg/mL, resp., indicating higher bacterial toxicity as ARGO is reduced. To uncover the GO toxicity mechanism, fluorescent dye-based assays were used to measure oxidative stress at the EC50. ARGO showed an increase in reactive oxygen species (ROS) whereas TGO500 and TGO800 increased fluorescein diacetate (FDA) by 30 and 42% indicating a decrease in cell permeability. Due to a possible wrapping mechanism, plating assays after a post-exposure sonication were performed to explain TGO's low oxidative response and high FDA levels. Results show no difference in colony forming units, indicating that cell entrapment and inhibition of cell growth by GO are present. By comparing different GO samples at their EC50, this study reveals that redn. of GO alter both the mechanisms of cellular interaction and the degree of toxicity to bacteria.
- 21Wang, Y.; Basdogan, Y.; Zhang, T.; Lankone, R. S.; Wallace, A. N.; Fairbrother, D. H.; Keith, J. A.; Gilbertson, L. M. Unveiling the Synergistic Role of Oxygen Functional Groups in the Graphene-Mediated Oxidation of Glutathione. ACS Appl. Mater. Interfaces 2020, 12 (41), 45753– 45762, DOI: 10.1021/acsami.0c11539Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVKht77J&md5=8a837a2b787110f9975339a1c1b2bca0Unveiling the Synergistic Role of Oxygen Functional Groups in the Graphene-Mediated Oxidation of GlutathioneWang, Yan; Basdogan, Yasemin; Zhang, Tianyu; Lankone, Ronald S.; Wallace, Alexa N.; Fairbrother, D. Howard; Keith, John A.; Gilbertson, Leanne M.ACS Applied Materials & Interfaces (2020), 12 (41), 45753-45762CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)This is the first report of an at.-scale direct oxidn. mechanism of the thiol group in glutathione (GSH) by epoxides on graphene oxide (GO) at room temp. The proposed reaction mechanism is detd. using a coupled exptl. and computational approach; active sites for the reaction are detd. through examn. of GO surface chem. changes before and after exposure to GSH, and d. functional theory (DFT) calcns. det. the reaction barriers for the possible GO-GSH reaction schemes. The findings build on the previously established catalytic mechanism of GSH oxidn. by graphenic nanocarbon surfaces and importantly identify the direct reaction mechanism which becomes important in low-oxygen environments. Exptl. results suggest epoxides as the active sites for the reaction with GSH, which we confirm using DFT calcns. of reaction barriers and further identify a synergism between the adjacent epoxide and hydroxyl groups on the GO surface. The direct oxidn. mechanism at specific oxygen sites offers insight into controlling GO chem. reactivity through surface chem. manipulations. This insight is crit. for furthering our understanding of GO oxidative stress pathways in cytotoxicity as well as for providing rational material design for GO applications that can leverage this reaction.
- 22Palmieri, V.; Bugli, F.; Lauriola, M. C.; Cacaci, M.; Torelli, R.; Ciasca, G.; Conti, C.; Sanguinetti, M.; Papi, M.; De Spirito, M. Bacteria Meet Graphene: Modulation of Graphene Oxide Nanosheet Interaction with Human Pathogens for Effective Antimicrobial Therapy. ACS Biomater. Sci. Eng. 2017, 3 (4), 619– 627, DOI: 10.1021/acsbiomaterials.6b00812Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXivFahtb4%253D&md5=a39b92526a6bad5c14c89b9c945e6df1Bacteria Meet Graphene: Modulation of Graphene Oxide Nanosheet Interaction with Human Pathogens for Effective Antimicrobial TherapyPalmieri, Valentina; Bugli, Francesca; Lauriola, Maria Carmela; Cacaci, Margherita; Torelli, Riccardo; Ciasca, Gabriele; Conti, Claudio; Sanguinetti, Maurizio; Papi, Massimiliano; De Spirito, MarcoACS Biomaterials Science & Engineering (2017), 3 (4), 619-627CODEN: ABSEBA; ISSN:2373-9878. (American Chemical Society)The development of new pharmacol. strategies that evade bacterial resistance became a compelling worldwide challenge. Graphene Oxide (GO) can represent the nanotechnol. answer being economic, easy to produce and to degrade and having multi-target specificity against bacteria. Several groups tried to define the interaction between GO sheets and human pathogens. Unfortunately, controversial results from inhibition to bacterial growth enhancement have been reported. The main difference among all expts. evidences relies on the environmental conditions adopted to study the bacteria-GO interaction. Indeed GO, stable in deionized water, undergoes to a rapid and salt-specific DLVO-like aggregation that influences antimicrobial effects. Considering this phenomenon, interaction of bacteria with GO aggregates having different size, morphol., and surface potential can create a complex scenario that explains the contrasting results reported so far. In this paper, we demonstrate that by modulating the GO stability in soln., the antibacterial or growth enhancement effect can be controlled on Staphylococcus aureus and Escherichia coli. GO at low concn. cut microorganisms membranes and, at high concn., forms complexes with pathogens and inhibits or enhances bacteria growth in a surface potential-dependent manner. With the framework defined in this study the clin. application of GO gets closer and controversial results in literature can be explained.
- 23Guo, Z.; Xie, C.; Zhang, P.; Zhang, J.; Wang, G.; He, X.; Ma, Y.; Zhao, B.; Zhang, Z. Toxicity and Transformation of Graphene Oxide and Reduced Graphene Oxide in Bacteria Biofilm. Sci. Total Environ. 2017, 580, 1300– 1308, DOI: 10.1016/j.scitotenv.2016.12.093Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitFehsrbM&md5=b44d5023f1950d0403a463e6b7efdee1Toxicity and transformation of graphene oxide and reduced graphene oxide in bacteria biofilmGuo, Zhiling; Xie, Changjian; Zhang, Peng; Zhang, Junzhe; Wang, Guohua; He, Xiao; Ma, Yuhui; Zhao, Bin; Zhang, ZhiyongScience of the Total Environment (2017), 580 (), 1300-1308CODEN: STENDL; ISSN:0048-9697. (Elsevier B.V.)Impact of graphene based material (GNMs) on bacteria biofilm has not been well understood yet. In this study, the authors compared the impact of graphene oxide (GO) and reduced graphene oxide (rGO) on biofilm formation and development in Luria-Bertani (LB) medium using Escherichia coli and Staphylococcus aureus as models. GO significantly enhanced the cell growth, biofilm formation, and biofilm development even up to a concn. of 500 mg/L. In contrast, rGO (≥50 mg/L) strongly inhibited cell growth and biofilm formation. However, the inhibitory effects of rGO (50 mg/L and 100 mg/L) were attenuated in the mature phase (>24 h) and eliminated at 48 h. GO at 250 mg/L decreased the reactive oxygen species (ROS) levels in biofilm and extracellular region at mature phase. ROS levels were significantly increased by rGO at early phase, while they returned to the same levels as control at mature phase. These results suggest that oxidative stress contributed to the inhibitory effect of rGO on bacterial biofilm. The authors further found that supplement of extracellular polymeric substances (EPS) in the growth medium attenuated the inhibitory effect of rGO on the growth of developed biofilm. XPS results showed that rGO were oxidized to GO which can enhance the bacterial growth. The authors deduced that the elimination of the toxicity of rGO at mature phase was contributed by EPS protection and the oxidn. of rGO. This study provides new insights into the interaction of GNMs with bacteria biofilm.
- 24Papageorgiou, D. G.; Kinloch, I. A.; Young, R. J. Mechanical Properties of Graphene and Graphene-Based Nanocomposites. Prog. Mater. Sci. 2017, 90, 75– 127, DOI: 10.1016/j.pmatsci.2017.07.004Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtlShur7I&md5=cc409f1fd4839f4540b5823bab880ffcMechanical properties of graphene and graphene-based nanocompositesPapageorgiou, Dimitrios G.; Kinloch, Ian A.; Young, Robert J.Progress in Materials Science (2017), 90 (), 75-127CODEN: PRMSAQ; ISSN:0079-6425. (Elsevier Ltd.)In this present review, the current status of the intrinsic mech. properties of the graphene-family of materials along with the prepn. and properties of bulk graphene-based nanocomposites is thoroughly examd. The usefulness of Raman spectroscopy for the characterization and study of the mech. properties of graphene flakes and their composites is clearly exhibited. Furthermore, the prepn. strategies of bulk graphene-based nanocomposites are discussed and the mech. properties of nanocomposites reported in the literature are analyzed. In particular, through the analyze of several hundred literature papers on graphene composites, we have found a unique correlation between the filler modulus, derived from the rule of mixts., and the composite matrix. This correlation is found to hold true across a wide range of polymer matrixes and thus suggests that the common assumption that the filler modulus is independent of the matric is incorrect, explaining the apparent under performance of graphene in some systems. The presence of graphene even at very low loadings can provide significant reinforcement to the final material, while the parameters that affect the nanocomposite strongly are thoroughly reviewed. Finally, the potential applications and future perspectives are discussed with regard to scale up capabilities and possible developments of graphene-based nanocomposite materials.
- 25Poulin, P.; Jalili, R.; Neri, W.; Nallet, F.; Divoux, T.; Colin, A.; Aboutalebi, S. H.; Wallace, G.; Zakri, C. Superflexibility of Graphene Oxide. Proc. Natl. Acad. Sci. U.S.A. 2016, 113 (40), 11088– 11093, DOI: 10.1073/pnas.1605121113Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFarsLbP&md5=a6691209062b9dc3c2f5c9b92b443de8Superflexibility of graphene oxidePoulin, Philippe; Jalili, Rouhollah; Neri, Wilfrid; Nallet, Frederic; Divoux, Thibaut; Colin, Annie; Aboutalebi, Seyed Hamed; Wallace, Gordon; Zakri, CecileProceedings of the National Academy of Sciences of the United States of America (2016), 113 (40), 11088-11093CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Graphene oxide (GO), the main precursor of graphene-based materials made by soln. processing, is known to be very stiff. Indeed, it has a Young's modulus comparable to steel, on the order of 300 GPa. Despite its very high stiffness, we show here that GO is superflexible. We quant. measure the GO bending rigidity by characterizing the flattening of thermal undulations in response to shear forces in soln. Characterizations are performed by the combination of synchrotron X-ray diffraction at small angles and in situ rheol. (rheo-SAXS) expts. using the high X-ray flux of a synchrotron source. The bending modulus is 1 kT, which is about two orders of magnitude lower than the bending rigidity of neat graphene. This superflexibility compares with the fluidity of self-assembled liq. bilayers. This behavior is discussed by considering the mechanisms at play in bending and stretching deformations of at. monolayers. The superflexibility of GO is a unique feature to develop bendable electronics after redn., films, coatings, and fibers. This unique combination of properties of GO allows for flexibility in processing and fabrication coupled with a robustness in the fabricated structure.
- 26Kumar, S.; Parekh, S. H. Linking Graphene-Based Material Physicochemical Properties with Molecular Adsorption, Structure and Cell Fate. Commun. Chem. 2020, 3 (1), 8, DOI: 10.1038/s42004-019-0254-9Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXktlynt7c%253D&md5=ec3f7c93c6f874c7a1de9f939f881a91Linking graphene-based material physicochemical properties with molecular adsorption, structure and cell fateKumar, Sachin; Parekh, Sapun H.Communications Chemistry (2020), 3 (1), 8CODEN: CCOHCT; ISSN:2399-3669. (Nature Research)A review. Abstr.: Graphene, an allotrope of carbon, consists of a single layer of carbon atoms with uniquely tuneable properties. As such, graphene-based materials (GBMs) have gained interest for tissue engineering applications. GBMs are often discussed in the context of how different physicochem. properties affect cell physiol., without explicitly considering the impact of adsorbed proteins. Establishing a relationship between graphene properties, adsorbed proteins, and cell response is necessary as these proteins provide the surface upon which cells attach and grow. This review highlights the mol. adsorption of proteins on different GBMs, protein structural changes, and the connection to cellular function.
- 27Wilson, C. J.; Clegg, R. E.; Leavesley, D. I.; Pearcy, M. J. Mediation of Biomaterial–Cell Interactions by Adsorbed Proteins: a Review. Tissue Eng. 2005, 11 (1–2), 1– 18, DOI: 10.1089/ten.2005.11.1Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhs12rt7g%253D&md5=e2bdb40542ef8ca45b4762a12e86ca06Mediation of Biomaterial-Cell Interactions by Adsorbed Proteins: A ReviewWilson, Cameron J.; Clegg, Richard E.; Leavesley, David I.; Pearcy, Mark J.Tissue Engineering (2005), 11 (1/2), 1-18CODEN: TIENFP; ISSN:1076-3279. (Mary Ann Liebert, Inc.)A review. An appropriate cellular response to implanted surfaces is essential for tissue regeneration and integration. It is well described that implanted materials are immediately coated with proteins from blood and interstitial fluids, and it is through this adsorbed layer that cells sense foreign surfaces. Hence, it is the adsorbed proteins, rather than the surface itself, to which cells initially respond. Diverse studies using a range of materials have demonstrated the pivotal role of extracellular adhesion proteins-fibronectin and vitronectin in particular-in cell adhesion, morphol., and migration. These events underlie the subsequent responses required for tissue repair, with the nature of cell surface interactions contributing to survival, growth, and differentiation. The pattern in which adhesion proteins and other bioactive mols. adsorb thus elicits cellular reactions specific to the underlying physicochem. properties of the material. Accordingly, in vitro studies generally demonstrate favorable cell responses to charged, hydrophilic surfaces, corresponding to superior adsorption and bioactivity of adhesion proteins. This review illustrates the mediation of cell responses to biomaterials by adsorbed proteins, in the context of osteoblasts and selected materials used in orthopedic implants and bone tissue engineering. It is recognized, however, that the periimplant environment in vivo will differ substantially from the cell-biomaterial interface in vitro. Hence, one of the key issues yet to be resolved is that of the interface compn. actually encountered by osteoblasts within the sequence of inflammation and bone regeneration.
- 28Vacchi, I. A.; Raya, J.; Bianco, A.; Ménard-Moyon, C. Controlled Derivatization of Hydroxyl Groups of Graphene Oxide in Mild Conditions. 2D Materials 2018, 5 (3), 035037, DOI: 10.1088/2053-1583/aac8a9Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXlt1Sjsb8%253D&md5=ffb48c68e472aa82f87bfd8e831ed140Controlled derivatization of hydroxyl groups of graphene oxide in mild conditionsVacchi, Isabella A.; Raya, Jesus; Bianco, Alberto; Menard-Moyon, Cecilia2D Materials (2018), 5 (3), 035037/1-035037/11CODEN: DMATB7; ISSN:2053-1583. (IOP Publishing Ltd.)Graphene oxide (GO) is constituted of various oxygen-contg. functionalities, primarily epoxides and hydroxyl groups on the basal plane, with a very low amt. of carbonyl, quinone, carboxylic acid, phenol, and lactone functions at the edges. The high chem. reactivity of these oxygenated groups makes functionalization difficult to control as different reactions can occur concomitantly. In this study we have investigated the reactivity of GO toward orthogonal reactions to selectively functionalize the hydroxyl groups, which are present in a high amt. We explored both the esterification and the Williamson reaction. Our strategies present the main advantage to occur in mild conditions, thus preserving the intrinsic properties of GO, whereas most reactions reported in literature require relatively harsh conditions, leading to (partial) redn., and/ or are not chemoselective. We have also extended our study to the ketones and examd. their derivatization by the Wittig reaction. This work has allowed developing two facile methods for the covalent derivatization of the hydroxyl groups in mild conditions, while GO was not reactive toward the Wittig reaction, probably due to the low amt. of ketones. Overall, this work leads to a better understanding of the reactivity of GO for controlled derivatization. This opens promising perspectives for multi-functionalization of GO in order to design graphene-based nanomaterials endowed of multiple properties.
- 29Simon-Deckers, A.; Loo, S.; Mayne-L’hermite, M.; Herlin-Boime, N.; Menguy, N.; Reynaud, C.; Gouget, B.; Carriere, M. Size-, Composition-and Shape-Dependent Toxicological Impact of Metal Oxide Nanoparticles and Carbon Nanotubes Toward Bacteria. Environ. Sci. Technol. 2009, 43 (21), 8423– 8429, DOI: 10.1021/es9016975Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXht1artbnJ&md5=4c7537ad2861aaf61ff103cd1a16e7b7Size-, Composition- and Shape-Dependent Toxicological Impact of Metal Oxide Nanoparticles and Carbon Nanotubes toward BacteriaSimon-Deckers, Angelique; Loo, Sylvain; Mayne-L'hermite, Martine; Herlin-Boime, Nathalie; Menguy, Nicolas; Reynaud, Cecile; Gouget, Barbara; Carriere, MarieEnvironmental Science & Technology (2009), 43 (21), 8423-8429CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)Ecotoxicol. effects of nanoparticles (NP) are still poorly documented while their commercialization for industrial and household applications increases. The aim of this study was to evaluate the influence of physicochem. characteristics on metal oxide NP and carbon nanotubes toxicol. effects toward bacteria. Two strains of bacteria, Cupriavidus metallidurans CH34 and Escherichia coli MG1655 were exposed to TiO2 or Al2O3 NP or to multiwalled-carbon nanotubes (MWCNT). Particular attention was paid on optimizing NP dispersion to obtain nonagglomerated suspensions. The authors' results show that NP toxicity depends on their chem. compn., size, surface charge, and shape but not on their cryst. phase. MWCNT toxicity does not depend on their purity. Toxicity also depends on the bacterial strain: E. coli MG1655 is sensitive to NP, whereas C. metallidurans CH34 is not. Interestingly, NP are accumulated in both bacterial strains, and assocn. between NP and bacteria is necessary for bacterial death to occur. NP may then represent a danger for the environment, causing the disappearance of some sensitive bacterial strains such as E. coli MG1655, but also being mobilized by nonsensitive strains such as C. metallidurans CH34 and transported through the whole ecosystem.
- 30Faserl, K.; Chetwynd, A. J.; Lynch, I.; Thorn, J. A.; Lindner, H. H. Corona Isolation Method Matters: Capillary Electrophoresis Mass Spectrometry Based Comparison of Protein Corona Compositions Following on-Particle Versus in-Solution or in-Gel Digestion. Nanomaterials 2019, 9 (6), 898, DOI: 10.3390/nano9060898Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsFehtL7L&md5=83b2559836f95e0e4a8da53034605450Corona isolation method matters: capillary electrophoresis mass spectrometry based comparison of protein corona compositions following on-particle versus in-solution or in-gel digestionFaserl, Klaus; Chetwynd, Andrew J.; Lynch, Iseult; Thorn, James A.; Lindner, Herbert H.Nanomaterials (2019), 9 (6), 898CODEN: NANOKO; ISSN:2079-4991. (MDPI AG)Increased understanding of the role of the nanomaterial protein corona in driving nanomaterial uptake into, and impacts on, cells and organisms, and the consequent need for characterization of the corona, has led to a flourishing of methods for isolation and anal. of the constituent proteins over the past decade. However, despite over 700 corona studies to date, very little is understood in terms of which methods provide the most precise and comprehensive characterization of the corona. With the increasing importance of the modeling of corona formation and its correlation with biol. impacts, it is timely to properly characterize and validate the isolation approaches used to det. the protein corona. The current work introduces Capillary Electrophoresis with Electro Spray Ionization Mass Spectrometry (CESI-MS) as a novel method for protein corona characterizations and develops an on-particle tryptic digestion method, comparing peptide solubilization solns. and characterizing the recovery of proteins from the nanomaterial surface. The CESI-MS was compared to the gold std. nano-LC-MS for corona anal. and maintained a high degree of reproducibility, while increasing throughput by >3-fold. These are important factors to consider when designing corona studies and modeling corona formation and impacts, highlighting the significance of a comprehensive validation of nanomaterial corona anal. methods.
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References
This article references 30 other publications.
- 1Hu, W.; Peng, C.; Luo, W.; Lv, M.; Li, X.; Li, D.; Huang, Q.; Fan, C. Graphene-Based Antibacterial Paper. ACS Nano 2010, 4 (7), 4317– 4323, DOI: 10.1021/nn101097v1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXotFKnur0%253D&md5=fe1dad454736c46ed1b4346f30f74743Graphene-Based Antibacterial PaperHu, Wenbing; Peng, Cheng; Luo, Weijie; Lv, Min; Li, Xiaoming; Li, Di; Huang, Qing; Fan, ChunhaiACS Nano (2010), 4 (7), 4317-4323CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Graphene is a monolayer of tightly packed carbon atoms that possesses many interesting properties and has numerous exciting applications. In this work, we report the antibacterial activity of two water-dispersible graphene derivs., graphene oxide (GO) and reduced graphene oxide (rGO) nanosheets. Such graphene-based nanomaterials can effectively inhibit the growth of Escherichia coli bacteria while showing minimal cytotoxicity. We have also demonstrated that macroscopic freestanding GO and rGO paper can be conveniently fabricated from their suspension via simple vacuum filtration. Given the superior antibacterial effect of GO and the fact that GO can be mass-produced and easily processed to make freestanding and flexible paper with low cost, we expect this new carbon nanomaterial may find important environmental and clin. applications.
- 2Liu, S.; Zeng, T. H.; Hofmann, M.; Burcombe, E.; Wei, J.; Jiang, R.; Kong, J.; Chen, Y. Antibacterial Activity of Graphite, Graphite Oxide, Graphene Oxide, and Reduced Graphene Oxide: Membrane and Oxidative Stress. ACS Nano 2011, 5 (9), 6971– 6980, DOI: 10.1021/nn202451x2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtVyls73L&md5=2b9a3ae97cc102efe556269af91473ebAntibacterial activity of graphite, graphite oxide, graphene oxide, and reduced graphene oxide: Membrane and oxidative stressLiu, Shao-Bin; Zeng, Ting-Ying Helen; Hofmann, Mario; Burcombe, Ehdi; Wei, Jun; Jiang, Rong-Rong; Kong, Jing; Chen, YuanACS Nano (2011), 5 (9), 6971-6980CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Health and environmental impacts of graphene-based materials need to be thoroughly evaluated before their potential applications. Graphene has strong cytotoxicity toward bacteria. To better understand its antimicrobial mechanism, we compared the antibacterial activity of four types of graphene-based materials (graphite (Gt), graphite oxide (GtO), graphene oxide (GO), and reduced graphene oxide (rGO)) toward a bacterial model: Escherichia coli. Under similar concn. and incubation conditions, GO dispersion shows the highest antibacterial activity, sequentially followed by rGO, Gt, and GtO. Scanning electron microscope (SEM) and dynamic light scattering analyses show that GO aggregates have the smallest av. size among the four types of materials. SEM images display that the direct contacts with graphene nanosheets disrupt cell membrane. No superoxide anion (O2·-) induced reactive oxygen species (ROS) prodn. is detected. However, the four types of materials can oxidize glutathione, which serves as redox state mediator in bacteria. Conductive rGO and Gt have higher oxidn. capacities than insulating GO and GtO. Results suggest that antimicrobial actions are contributed by both membrane and oxidn. stress. We propose that a three-step antimicrobial mechanism, previously used for carbon nanotubes, is applicable to graphene-based materials. It includes initial cell deposition on graphene-based materials, membrane stress caused by direct contact with sharp nanosheets, and the ensuing superoxide anion-independent oxidn. The authors envision that physicochem. properties of graphene-based materials, such as d. of functional groups, size, and cond., can be precisely tailored to either reducing their health and environmental risks or increasing their application potentials.
- 3Perreault, F.; De Faria, A. F.; Nejati, S.; Elimelech, M. Antimicrobial Properties of Graphene Oxide Nanosheets: Why Size Matters. ACS Nano 2015, 9 (7), 7226– 7236, DOI: 10.1021/acsnano.5b020673https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtVKitr%252FM&md5=ad57b32363cd9aa20c99fb374d484634Antimicrobial Properties of Graphene Oxide Nanosheets: Why Size MattersPerreault, Francois; Fonseca de Faria, Andreia; Nejati, Siamak; Elimelech, MenachemACS Nano (2015), 9 (7), 7226-7236CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Graphene oxide (GO) is a promising material for the development of antimicrobial surfaces due to its contact-based antimicrobial activity. However, the relationship between GO physicochem. properties and its antimicrobial activity has yet to be elucidated. In this study, we investigated the size-dependency of GO antimicrobial activity using the Gram-neg. bacteria Escherichia coli. GO suspensions of av. sheet area ranging from 0.01 to 0.65 μm2 were produced and their antimicrobial activity evaluated in cell suspensions or as a model GO surface coating. The antimicrobial activity of GO surface coatings increased 4-fold when GO sheet area decreased from 0.65 to 0.01 μm2. The higher antimicrobial effect of smaller GO sheets is attributed to oxidative mechanisms assocd. with the higher defect d. of smaller sheets. In contrast, in suspension assays, GO interacted with bacteria in a cell entrapment mechanism; in this case, the antimicrobial effect of GO increased with increasing sheet area, with apparent complete inactivation obsd. for the 0.65 μm2 sheets after a 3 h exposure. However, cell inactivation by GO entrapment was reversible and all initially viable cells could be recovered when sepd. from GO sheets by sonication. These findings provide useful guidelines for future development of graphene-based antimicrobial surface coatings, where smaller sheet sizes can increase the antimicrobial activity of the material. Our study further emphasizes the importance of an accurate assessment of the antimicrobial effect of nanomaterials when used for antimicrobial surface design.
- 4Zhao, J.; Deng, B.; Lv, M.; Li, J.; Zhang, Y.; Jiang, H.; Peng, C.; Li, J.; Shi, J.; Huang, Q. Graphene Oxide-Based Antibacterial Cotton Fabrics. Adv. Healthc. Mater. 2013, 2 (9), 1259– 1266, DOI: 10.1002/adhm.2012004374https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVSlsL3K&md5=b59829e8096c3759d9c1762abf530272Graphene Oxide-Based Antibacterial Cotton FabricsZhao, Jinming; Deng, Bo; Lv, Min; Li, Jingye; Zhang, Yujie; Jiang, Haiqing; Peng, Cheng; Li, Jiang; Shi, Jiye; Huang, Qing; Fan, ChunhaiAdvanced Healthcare Materials (2013), 2 (9), 1259-1266CODEN: AHMDBJ; ISSN:2192-2640. (Wiley-VCH Verlag GmbH & Co. KGaA)Graphene oxide (GO) is an excellent bacteria-killing nanomaterial. In this work, macroscopic applications of this promising nanomaterial by fixing GO sheets onto cotton fabrics, which possess strong antibacterial property and great laundering durability, are reported. The GO-based antibacterial cotton fabrics are prepd. in 3 ways: direct adsorption, radiation-induced crosslinking, and chem. crosslinking. Antibacterial tests show that all these GO-contg. fabrics possess strong antibacterial property and could inactivate 98% of bacteria. Most significantly, these fabrics can still kill >90% bacteria even after being washed for 100 times. Also importantly, animal tests show that GO-modified cotton fabrics cause no irritation to rabbit skin. Hence, it is believed that these flexible, foldable, and re-usable GO-based antibacterial cotton fabrics have high promise as a type of new nano-engineered antibacterial materials for a wide range of applications.
- 5Qiu, J.; Liu, L.; Zhu, H.; Liu, X. Combination Types Between Graphene Oxide and Substrate Affect the Antibacterial Activity. Bioact. Mater. 2018, 3 (3), 341– 346, DOI: 10.1016/j.bioactmat.2018.05.0015https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c%252FmtlKquw%253D%253D&md5=26758333f4a72563766d1a0a02ca3b52Combination types between graphene oxide and substrate affect the antibacterial activityQiu Jiajun; Liu Lu; Zhu Hongqin; Liu Xuanyong; Qiu Jiajun; Liu LuBioactive materials (2018), 3 (3), 341-346 ISSN:.Duo to their superior physicochemical properties, graphene and its derivatives (GDs), such as graphene oxide (GO) and reduced graphene oxide (rGO), have attracted extensive research interests around the world. In recent years, antibacterial activities of GDs have aroused wide concern and substantial works have been done. However, the underlying antibacterial mechanisms still remain controversial. Antibacterial activities of GDs vary with various factors, such as size, number of layers, oxygen-containing groups, and experimental surroundings. We assume that combination types between graphene oxide and substrate may affect the antibacterial activity. Therefore, in this work, GO was fixed on the titanium surface with three kinds of combination types including drop with gravitational effects (GO-D), electrostatic interaction (GO-APS) and electrophoretic deposition (GO-EPD), and the antibacterial activities in vitro were systematically investigated. Results showed that combination types affected the ability of GO for preventing Staphylococcus aureus (S. aureus) from gathering, sharpness of wrinkles or edges and reactive oxygen spices (ROS) levels. Once S. aureus are in the form of separation without aggregation, GO can effectively interact with them and kill them with sharp wrinkles or edges and high ROS levels. GO-EPD could effectively prevent S. aureus from gathering, own sharp wrinkles or edges and could generate higher ROS levels. As a result, GO-EPD exhibited optimal antibacterial activity against S. aureus, followed by GO-APS and GO-D.
- 6Graphene air filter mask developed in China, March 31, 2017. https://www.2dmaterialsmag.com/graphene-air-filter-mask-developed-in-china/ (accessed February 2023).There is no corresponding record for this reference.
- 7Seo, D. H.; Pineda, S.; Woo, Y. C.; Xie, M.; Murdock, A. T.; Ang, E. Y.; Jiao, Y.; Park, M. J.; Lim, S. I.; Lawn, M. Anti-Fouling Graphene-Based Membranes for Effective Water Desalination. Nat. Commun. 2018, 9 (1), 8, DOI: 10.1038/s41467-018-02871-3There is no corresponding record for this reference.
- 8Fadeel, B.; Bussy, C.; Merino, S.; Vázquez, E.; Flahaut, E.; Mouchet, F.; Evariste, L.; Gauthier, L.; Koivisto, A. J.; Vogel, U. Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment. ACS Nano 2018, 12 (11), 10582– 10620, DOI: 10.1021/acsnano.8b047588https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXitVyju7nN&md5=f276495b7b3b777acedf279460618b25Safety Assessment of Graphene-Based Materials: Focus on Human Health and the EnvironmentFadeel, Bengt; Bussy, Cyrill; Merino, Sonia; Vazquez, Ester; Flahaut, Emmanuel; Mouchet, Florence; Evariste, Lauris; Gauthier, Laury; Koivisto, Antti J.; Vogel, Ulla; Martin, Cristina; Delogu, Lucia G.; Buerki-Thurnherr, Tina; Wick, Peter; Beloin-Saint-Pierre, Didier; Hischier, Roland; Pelin, Marco; Candotto Carniel, Fabio; Tretiach, Mauro; Cesca, Fabrizia; Benfenati, Fabio; Scaini, Denis; Ballerini, Laura; Kostarelos, Kostas; Prato, Maurizio; Bianco, AlbertoACS Nano (2018), 12 (11), 10582-10620CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)A review. Graphene and its derivs. are heralded as "miracle" materials with manifold applications in different sectors of society from electronics to energy storage to medicine. The increasing exploitation of graphene-based materials (GBMs) necessitates a comprehensive evaluation of the potential impact of these materials on human health and the environment. Here, we discuss synthesis and characterization of GBMs as well as human and environmental hazard assessment of GBMs using in vitro and in vivo model systems with the aim to understand the properties that underlie the biol. effects of these materials; not all GBMs are alike, and it is essential that we disentangle the structure-activity relationships for this class of materials.
- 9Hegab, H. M.; ElMekawy, A.; Zou, L.; Mulcahy, D.; Saint, C. P.; Ginic-Markovic, M. The Controversial Antibacterial Activity of Graphene-Based Materials. Carbon 2016, 105, 362– 376, DOI: 10.1016/j.carbon.2016.04.0469https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xntlyntbc%253D&md5=d673e60450126e3f4ec9d9d2e0f9b74fThe controversial antibacterial activity of graphene-based materialsHegab, Hanaa M.; El Mekawy, Ahmed; Zou, Linda; Mulcahy, Dennis; Saint, Christopher P.; Ginic-Markovic, MilenaCarbon (2016), 105 (), 362-376CODEN: CRBNAH; ISSN:0008-6223. (Elsevier Ltd.)A review. Graphene (Gr)-based materials are a promising nanomaterial for the development of antibacterial surfaces owing to their biocidal activity. However, the effect of the physicochem. features of these materials on their antibacterial activity has yet to be clarified. Gr-based nanomaterials can interact with cellular components, e.g. membranes, proteins and DNA, and initiate a sequence of nanomaterials/bacterial interactions that rely on colloidal energies and active bio-physicochem. interfaces. Analyzing these different interfaces permits the development of anticipated relations between phys./chem. structure and bactericidal activity depending on Gr-based nanomaterial features such as shape, size, hydrophilicity, roughness and functionality. Realizing how nanomaterials are interacting with bacterial cell membranes is correlated to how they affect bactericidal activity and is thus crit. for obtaining benign applications. This review anal. discusses specific Gr-based material features related to bacterial interactions, with special focus on the different modes of interaction between Gr-based materials and cell membranes, nucleic acids and lipid bilayers.
- 10Zou, X.; Zhang, L.; Wang, Z.; Luo, Y. Mechanisms of the Antimicrobial Activities of Graphene Materials. J. Am. Chem. Soc. 2016, 138 (7), 2064– 2077, DOI: 10.1021/jacs.5b1141110https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhslKlsrk%253D&md5=397d63d0aae7bd3d4ca584cd34d00decMechanisms of the Antimicrobial Activities of Graphene MaterialsZou, Xuefeng; Zhang, Li; Wang, Zhaojun; Luo, YangJournal of the American Chemical Society (2016), 138 (7), 2064-2077CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A thorough understanding of the antimicrobial mechanisms of graphene materials (GMs) is crit. to the manipulation of highly efficient antimicrobial nanomaterials for future biomedical applications. Here we review the most recent studies of GM-mediated antimicrobial properties. This review covers the physicochem. properties of GMs, exptl. surroundings, and selected microorganisms as well as the interaction between GMs and selected microorganisms to explore controversial antimicrobial activities. Finally, we rationally analyze the strengths and weaknesses of the proposed mechanisms and provide new insights into the remaining challenges and perspectives for future studies.
- 11Tu, Y.; Lv, M.; Xiu, P.; Huynh, T.; Zhang, M.; Castelli, M.; Liu, Z.; Huang, Q.; Fan, C.; Fang, H. Destructive Extraction of Phospholipids from Escherichia Coli Membranes by Graphene Nanosheets. Nat. Nanotechnol. 2013, 8 (8), 594– 601, DOI: 10.1038/nnano.2013.12511https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVKhtL7O&md5=7f60957a5cc3b8008520ab5aeb9858adDestructive extraction of phospholipids from Escherichia coli membranes by graphene nanosheetsTu, Yusong; Lv, Min; Xiu, Peng; Huynh, Tien; Zhang, Meng; Castelli, Matteo; Liu, Zengrong; Huang, Qing; Fan, Chunhai; Fang, Haiping; Zhou, RuhongNature Nanotechnology (2013), 8 (8), 594-601CODEN: NNAABX; ISSN:1748-3387. (Nature Publishing Group)Understanding how nanomaterials interact with cell membranes is related to how they cause cytotoxicity and is therefore crit. for designing safer biomedical applications. Recently, graphene (a two-dimensional nanomaterial) was shown to have antibacterial activity on Escherichia coli, but its underlying mol. mechanisms remain unknown. Here we show exptl. and theor. that pristine graphene and graphene oxide nanosheets can induce the degrdn. of the inner and outer cell membranes of Escherichia coli, and reduce their viability. TEM shows three rough stages, and mol. dynamics simulations reveal the at. details of the process. Graphene nanosheets can penetrate into and ext. large amts. of phospholipids from the cell membranes because of the strong dispersion interactions between graphene and lipid mols. This destructive extn. offers a novel mechanism for the mol. basis of graphene's cytotoxicity and antibacterial activity.
- 12Li, Y.; Yuan, H.; von Dem Bussche, A.; Creighton, M.; Hurt, R. H.; Kane, A. B.; Gao, H. Graphene Microsheets Enter Cells Through Spontaneous Membrane Penetration at Edge Asperities and Corner Sites. Proc. Natl. Acad. Sci. U.S.A. 2013, 110 (30), 12295– 12300, DOI: 10.1073/pnas.122227611012https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1emu7vL&md5=6857eb72d9a20857dfd8b5f6f6c491a7Graphene microsheets enter cells through spontaneous membrane penetration at edge asperities and corner sitesLi, Yinfeng; Yuan, Hongyan; von dem Bussche, Annette; Creighton, Megan; Hurt, Robert H.; Kane, Agnes B.; Gao, HuajianProceedings of the National Academy of Sciences of the United States of America (2013), 110 (30), 12295-12300,S12295/1-S12295/11CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Understanding and controlling the interaction of graphene-based materials with cell membranes is key to the development of graphene-enabled biomedical technologies and to the management of graphene health and safety issues. Very little is known about the fundamental behavior of cell membranes exposed to ultrathin 2D synthetic materials. Here we investigate the interactions of graphene and few-layer graphene (FLG) microsheets with three cell types and with model lipid bilayers by combining coarse-grained mol. dynamics (MD), all-atom MD, anal. modeling, confocal fluorescence imaging, and electron microscopic imaging. The imaging expts. show edge-first uptake and complete internalization for a range of FLG samples of 0.5- to 10-μm lateral dimension. In contrast, the simulations show large energy barriers relative to kBT for membrane penetration by model graphene or FLG microsheets of similar size. More detailed simulations resolve this paradox by showing that entry is initiated at corners or asperities that are abundant along the irregular edges of fabricated graphene materials. Local piercing by these sharp protrusions initiates membrane propagation along the extended graphene edge and thus avoids the high energy barrier calcd. in simple idealized MD simulations. We propose that this mechanism allows cellular uptake of even large multilayer sheets of micrometer-scale lateral dimension, which is consistent with our multimodal bioimaging results for primary human keratinocytes, human lung epithelial cells, and murine macrophages.
- 13Lu, X.; Feng, X.; Werber, J. R.; Chu, C.; Zucker, I.; Kim, J.-H.; Osuji, C. O.; Elimelech, M. Enhanced Antibacterial Activity Through the Controlled Alignment of Graphene Oxide Nanosheets. Proc. Natl. Acad. Sci. U.S.A. 2017, 114 (46), E9793– E9801, DOI: 10.1073/pnas.171099611413https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslagtbvJ&md5=31b1dc68115ba48371cb8836d9f54b97Enhanced antibacterial activity through the controlled alignment of graphene oxide nanosheetsLu, Xinglin; Feng, Xunda; Werber, Jay R.; Chu, Chiheng; Zucker, Ines; Kim, Jae-Hong; Osuji, Chinedum O.; Elimelech, MenachemProceedings of the National Academy of Sciences of the United States of America (2017), 114 (46), E9793-E9801CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)The cytotoxicity of 2D graphene-based nanomaterials (GBNs) is highly important for engineered applications and environmental health. However, the isotropic orientation of GBNs, most notably graphene oxide (GO), in previous exptl. studies obscured the interpretation of cytotoxic contributions of nanosheet edges. Here, we investigate the orientation-dependent interaction of GBNs with bacteria using GO composite films. To produce the films, GO nanosheets are aligned in a magnetic field, immobilized by crosslinking of the surrounding matrix, and exposed on the surface through oxidative etching. Characterization by small-angle X-ray scattering and at. force microscopy confirms that GO nanosheets align progressively well with increasing magnetic field strength and that the alignment is effectively preserved by crosslinking. When contacted with the model bacterium Escherichia coli, GO nanosheets with vertical orientation exhibit enhanced antibacterial activity compared with random and horizontal orientations. Further characterization is performed to explain the enhanced antibacterial activity of the film with vertically aligned GO. Using phospholipid vesicles as a model system, we observe that GO nanosheets induce phys. disruption of the lipid bilayer. Addnl., we find substantial GO-induced oxidn. of glutathione, a model intracellular antioxidant, paired with limited generation of reactive oxygen species, suggesting that oxidn. occurs through a direct electron-transfer mechanism. These phys. and chem. mechanisms both require nanosheet penetration of the cell membrane, suggesting that the enhanced antibacterial activity of the film with vertically aligned GO stems from an increased d. of edges with a preferential orientation for membrane disruption. The importance of nanosheet penetration for cytotoxicity has direct implications for the design of engineering surfaces using GBNs.
- 14Mejías Carpio, I. E.; Santos, C. M.; Wei, X.; Rodrigues, D. F. Toxicity of a Polymer–Graphene Oxide Composite Against Bacterial Planktonic Cells, Biofilms, and Mammalian Cells. Nanoscale 2012, 4 (15), 4746– 4756, DOI: 10.1039/c2nr30774j14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVSqt7rK&md5=37a4406506d358ada320fce50c410c9cToxicity of a polymer-graphene oxide composite against bacterial planktonic cells, biofilms, and mammalian cellsMejias Carpio, Isis E.; Santos, Catherine M.; Wei, Xin; Rodrigues, Debora F.Nanoscale (2012), 4 (15), 4746-4756CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)It is crit. to develop highly effective antimicrobial agents that are not harmful to humans and do not present adverse effects on the environment. Although antimicrobial studies of graphene-based nanomaterials are still quite limited, some researchers have paid particular attention to such nanocomposites as promising candidates for the next generation of antimicrobial agents. The polyvinyl-N-carbazole (PVK)-graphene oxide (GO) nanocomposite (PVK-GO), which contains only 3 wt% of GO well-dispersed in a 97 wt% PVK matrix, presents excellent antibacterial properties without significant cytotoxicity to mammalian cells. The high polymer content in this nanocomposite makes future large-scale material manufg. possible in a high-yield process of adiabatic bulk polymn. In this study, the toxicity of PVK-GO was assessed with planktonic microbial cells, biofilms, and NIH 3T3 fibroblast cells. The antibacterial effects were evaluated against 2 Gram-neg. bacteria: Escherichia coli and Cupriavidus metallidurans; and 2 Gram-pos. bacteria: Bacillus subtilis and Rhodococcus opacus. The results show that the PVK-GO nanocomposite presents higher antimicrobial effects than the pristine GO. The effectiveness of the PVK-GO in soln. was demonstrated as the nanocomposite "encapsulated" the bacterial cells, which led to reduced microbial metabolic activity and cell death. The fact that the PVK-GO did not present significant cytotoxicity to fibroblast cells offers a great opportunity for potential applications in important biomedical and industrial fields.
- 15Mangadlao, J. D.; Santos, C. M.; Felipe, M. J. L.; de Leon, A. C. C.; Rodrigues, D. F.; Advincula, R. C. On the Antibacterial Mechanism of Graphene Oxide (GO) Langmuir–Blodgett Films. Chem. Commun. 2015, 51 (14), 2886– 2889, DOI: 10.1039/C4CC07836E15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXitFegtr3E&md5=145624f5f2cdb4f7da6cf4949c2374c5On the antibacterial mechanism of graphene oxide (GO) Langmuir-Blodgett filmsMangadlao, J. D.; Santos, C. M.; Felipe, M. J. L.; de Leon, A. C. C.; Rodrigues, D. F.; Advincula, R. C.Chemical Communications (Cambridge, United Kingdom) (2015), 51 (14), 2886-2889CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)The Langmuir-Blodgett (LB) technique was used to immobilize flat graphene oxide (GO) sheets on a PET substrate to ascertain as to whether the edges of GO play an integral part in its antimicrobial mechanism. The obsd. antibacterial activity suggests that contact with the edges is not a fundamental part of the mechanism.
- 16Zucker, I.; Werber, J. R.; Fishman, Z. S.; Hashmi, S. M.; Gabinet, U. R.; Lu, X.; Osuji, C. O.; Pfefferle, L. D.; Elimelech, M. Loss of Phospholipid Membrane Integrity Induced by Two-Dimensional Nanomaterials. Environ. Sci. Technol. Lett. 2017, 4 (10), 404– 409, DOI: 10.1021/acs.estlett.7b0035816https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsVKmtb7F&md5=7e5c90f397af8b520af0b381359a6bf5Loss of Phospholipid Membrane Integrity Induced by Two-Dimensional NanomaterialsZucker, Ines; Werber, Jay R.; Fishman, Zachary S.; Hashmi, Sara M.; Gabinet, Uri R.; Lu, Xinglin; Osuji, Chinedum O.; Pfefferle, Lisa D.; Elimelech, MenachemEnvironmental Science & Technology Letters (2017), 4 (10), 404-409CODEN: ESTLCU; ISSN:2328-8930. (American Chemical Society)The interaction of two-dimensional (2D) nanomaterials with biol. membranes has important implications for ecotoxicity and human health. In this study, the authors use a dye-leakage assay to quant. assess the disruption of a model phospholipid bilayer membrane (i.e., lipid vesicles) by five emerging 2D nanomaterials: graphene oxide (GO), reduced graphene oxide (rGO), molybdenum disulfide (MoS2), copper oxide (CuO), and iron oxide (α-Fe2O3). Leakage of dye from the vesicle inner soln., which indicates loss of membrane integrity, was obsd. for GO, rGO, and MoS2 nanosheets but not for CuO and α-Fe2O3, implying that 2D morphol. by itself is not sufficient to cause loss of membrane integrity. Mixing GO and rGO with lipid vesicles induced aggregation, whereas enhanced stability (dispersion) was obsd. with MoS2 nanosheets, suggesting different aggregation mechanisms for the 2D nanomaterials upon interaction with lipid bilayers. No loss of membrane integrity was obsd. under strong oxidative conditions, indicating that nanosheet-driven membrane disruption stemmed from a phys. mechanism rather than chem. oxidn. For GO, the most disruptive nanomaterial, the authors show that the extent of membrane integrity loss was dependent on total surface area, not edge length, which is consistent with a lipid-extn. mechanism and inconsistent with a piercing mechanism.
- 17Xie, C.; Zhang, P.; Guo, Z.; Li, X.; Pang, Q.; Zheng, K.; He, X.; Ma, Y.; Zhang, Z.; Lynch, I. Elucidating the Origin of the Surface Functionalization-Dependent Bacterial Toxicity of Graphene Nanomaterials: Oxidative Damage, Physical Disruption, and Cell Autolysis. Sci. Total Environ. 2020, 747, 141546, DOI: 10.1016/j.scitotenv.2020.14154617https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsFykurvJ&md5=8cb7b85b78ed9ae62470baf21c95118dElucidating the origin of the surface functionalization - dependent bacterial toxicity of graphene nanomaterials: Oxidative damage, physical disruption, and cell autolysisXie, Changjian; Zhang, Peng; Guo, Zhiling; Li, Xiaowei; Pang, Qiuxiang; Zheng, Kang; He, Xiao; Ma, Yuhui; Zhang, Zhiyong; Lynch, IseultScience of the Total Environment (2020), 747 (), 141546CODEN: STENDL; ISSN:0048-9697. (Elsevier B.V.)Previous studies have shown that the toxicity of graphene nanomaterials (GNMs) to bacteria are related to the surface functionalization, however, the involved mechanisms are not fully understood. The present study aims to explore the toxic mechanisms of differentially functionalized GNMs to bacteria from the aspects of phys. interaction, oxidative damage and cell autolysis. Three basic functionalization of GNMs including carboxylation (G-COOH), hydroxylation (G-OH) and amination (G-NH2) were studied. G-COOH (66% viability vs. CT group) and G-OH (54%) graphene showed higher toxicity to E. coli than G-NH2 (96%) within 3 h at a concn. of 50 mg/L. The three materials showed distinct phys. interaction modes with bacterial cells. G-COOH and G-OH contact with cell membrane via their sharp edges thus causing more damage than G-NH2 which covered the bacteria attaching along the basal plane. The three GNMs showed similar radical generation capacities, thus the direct generation of radicals is not the mechanism causing the toxicity. Instead, the GNMs can oxidize the cellular antioxidant glutathione (GSH) thereby causing oxidative damage. The oxidative capacity follows the order: G-COOH > G-OH > G-NH2, which correlated with the antibacterial activity. Cell autolysis, the degrdn. of cell wall component peptidoglycan, was found to be a new mechanism inducing the death of bacteria. G-COOH and G-OH caused more cell autolysis than G-NH2, which accounts partially for the different toxicity of the three GNMs. The findings provide significant insights into the mechanism of GNMs toxicity to bacteria for not only the risk assessment of GNMs but also the design of graphene based antibacterial materials.
- 18Hou, W.-C.; Lee, P.-L.; Chou, Y.-C.; Wang, Y.-S. Antibacterial Property of Graphene Oxide: the Role of Phototransformation. Environ. Sci. Nano 2017, 4 (3), 647– 657, DOI: 10.1039/C6EN00427J18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXltlCnsA%253D%253D&md5=44ef2d666618d6f26f135ad6bfc57423Antibacterial property of graphene oxide: the role of phototransformationHou, Wen-Che; Lee, Pei-Ling; Chou, Yu-Chieh; Wang, Yi-ShengEnvironmental Science: Nano (2017), 4 (3), 647-657CODEN: ESNNA4; ISSN:2051-8161. (Royal Society of Chemistry)Graphene-related materials are emerging with a wide range of potential applications. Their possible ecol. effect must be properly evaluated before their widespread use. This study examd. the antibacterial activity of graphene oxide (GO) before and after solar transformation under two reaction scenarios. GO was directly phototransformed under simulated sunlight or indirectly photolyzed by photochem. generated hydroxyl radical (̇ OH). The results indicate that compared to parent GO, directly phototransformed GO showed increased toxicity to bacteria, while the indirectly phototransformed GO became less toxic. The reduced bacterial toxicity of indirectly photolyzed GO correlated with its large decrease in total org. carbon (TOC) concn. after the indirect photoreaction. In contrast, the directly phototransformed GO caused greater membrane disruption and oxidative stress, which is consistent with its increased antibacterial activity. The oxidative stress was likely assocd. with the intrinsic oxidn. capability of the directly photolyzed GO. Given that direct photolysis of GO is expected to occur more rapidly in sunlit surface waters, as predicted in previous research, enhanced antibacterial activity of phototransformed GO will likely dominate the initial solar transformation of GO, while microbial toxicity will decrease in long term photolysis where GO is extensively decompd. bẏ OH-mediated photoreaction.
- 19Vecitis, C. D.; Zodrow, K. R.; Kang, S.; Elimelech, M. Electronic-Structure-Dependent Bacterial Cytotoxicity of Single-Walled Carbon Nanotubes. ACS Nano 2010, 4 (9), 5471– 5479, DOI: 10.1021/nn101558x19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtFSlsrjE&md5=8ed380e81d17ed28a7dd52e81f026625Electronic-Structure-Dependent Bacterial Cytotoxicity of Single-Walled Carbon NanotubesVecitis, Chad D.; Zodrow, Katherine R.; Kang, Seoktae; Elimelech, MenachemACS Nano (2010), 4 (9), 5471-5479CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Single-walled carbon nanotubes (SWNTs) have been previously obsd. to be strong antimicrobial agents, and SWNT coatings can significantly reduce biofilm formation. However, the SWNT antimicrobial mechanism is not fully understood. Previous studies on SWNT cytotoxicity have concluded that membrane stress (i.e., direct SWNT-bacteria contact resulting in membrane perturbation and the release of intracellular contents) was the primary cause of cell death. Gene expression studies have indicated oxidative stress may be active, as well. Here, it is demonstrated for the first time how SWNT electronic structure (i.e., metallic vs. semiconducting) is a key factor regulating SWNT antimicrobial activity. Expts. were performed with well-characterized SWNTs of similar length and diam. but varying fraction of metallic nanotubes. Loss of Escherichia coli viability was obsd. to increase with an increasing fraction of metallic SWNTs. Time-dependent cytotoxicity measurements indicated that in all cases the majority of the SWNT antimicrobial action occurs shortly after (<15 min) bacteria-SWNT contact. The SWNT toxicity mechanism was investigated by in vitro SWNT-mediated oxidn. of glutathione, a common intracellular thiol that serves as an antioxidant and redox state mediator. The extent of glutathione oxidn. was obsd. to increase with increasing fraction of metallic SWNTs, indicating an elevated role of oxidative stress. SEM images of E. coli in contact with the SWNTs demonstrated electronic structure-dependent morphol. changes consistent with cytotoxicity and glutathione oxidn. results. A three-step SWNT antimicrobial mechanism is proposed involving (i) initial SWNT-bacteria contact, (ii) perturbation of the cell membrane, and (ii) electronic structure-dependent bacterial oxidn.
- 20Barrios, A. C.; Wang, Y.; Gilbertson, L. M.; Perreault, F. Structure–Property–Toxicity Relationships of Graphene Oxide: Role of Surface Chemistry on the Mechanisms of Interaction with Bacteria. Environ. Sci. Technol. 2019, 53 (24), 14679– 14687, DOI: 10.1021/acs.est.9b0505720https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXitFWlsrzN&md5=93afc64dd4f61e486fdb6d03774bc942Structure-Property-Toxicity Relationships of Graphene Oxide: Role of Surface Chemistry on the Mechanisms of Interaction with BacteriaBarrios, Ana C.; Wang, Yan; Gilbertson, Leanne M.; Perreault, FrancoisEnvironmental Science & Technology (2019), 53 (24), 14679-14687CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)Graphene oxide (GO) is an antimicrobial with tunable surface chem. To identify the physicochem. determinants of GO's antimicrobial activity, we generated different modified Hummer's GO materials thermally annealed (at 200, 500, or 800 °C) to modify the surface oxygen groups. The plating assays show that as received GO (ARGO) and TGO200, TGO500 and TGO800 reduce E. coli viability by 50% (EC50) at 183, 143, 127 and 86 μg/mL, resp., indicating higher bacterial toxicity as ARGO is reduced. To uncover the GO toxicity mechanism, fluorescent dye-based assays were used to measure oxidative stress at the EC50. ARGO showed an increase in reactive oxygen species (ROS) whereas TGO500 and TGO800 increased fluorescein diacetate (FDA) by 30 and 42% indicating a decrease in cell permeability. Due to a possible wrapping mechanism, plating assays after a post-exposure sonication were performed to explain TGO's low oxidative response and high FDA levels. Results show no difference in colony forming units, indicating that cell entrapment and inhibition of cell growth by GO are present. By comparing different GO samples at their EC50, this study reveals that redn. of GO alter both the mechanisms of cellular interaction and the degree of toxicity to bacteria.
- 21Wang, Y.; Basdogan, Y.; Zhang, T.; Lankone, R. S.; Wallace, A. N.; Fairbrother, D. H.; Keith, J. A.; Gilbertson, L. M. Unveiling the Synergistic Role of Oxygen Functional Groups in the Graphene-Mediated Oxidation of Glutathione. ACS Appl. Mater. Interfaces 2020, 12 (41), 45753– 45762, DOI: 10.1021/acsami.0c1153921https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVKht77J&md5=8a837a2b787110f9975339a1c1b2bca0Unveiling the Synergistic Role of Oxygen Functional Groups in the Graphene-Mediated Oxidation of GlutathioneWang, Yan; Basdogan, Yasemin; Zhang, Tianyu; Lankone, Ronald S.; Wallace, Alexa N.; Fairbrother, D. Howard; Keith, John A.; Gilbertson, Leanne M.ACS Applied Materials & Interfaces (2020), 12 (41), 45753-45762CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)This is the first report of an at.-scale direct oxidn. mechanism of the thiol group in glutathione (GSH) by epoxides on graphene oxide (GO) at room temp. The proposed reaction mechanism is detd. using a coupled exptl. and computational approach; active sites for the reaction are detd. through examn. of GO surface chem. changes before and after exposure to GSH, and d. functional theory (DFT) calcns. det. the reaction barriers for the possible GO-GSH reaction schemes. The findings build on the previously established catalytic mechanism of GSH oxidn. by graphenic nanocarbon surfaces and importantly identify the direct reaction mechanism which becomes important in low-oxygen environments. Exptl. results suggest epoxides as the active sites for the reaction with GSH, which we confirm using DFT calcns. of reaction barriers and further identify a synergism between the adjacent epoxide and hydroxyl groups on the GO surface. The direct oxidn. mechanism at specific oxygen sites offers insight into controlling GO chem. reactivity through surface chem. manipulations. This insight is crit. for furthering our understanding of GO oxidative stress pathways in cytotoxicity as well as for providing rational material design for GO applications that can leverage this reaction.
- 22Palmieri, V.; Bugli, F.; Lauriola, M. C.; Cacaci, M.; Torelli, R.; Ciasca, G.; Conti, C.; Sanguinetti, M.; Papi, M.; De Spirito, M. Bacteria Meet Graphene: Modulation of Graphene Oxide Nanosheet Interaction with Human Pathogens for Effective Antimicrobial Therapy. ACS Biomater. Sci. Eng. 2017, 3 (4), 619– 627, DOI: 10.1021/acsbiomaterials.6b0081222https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXivFahtb4%253D&md5=a39b92526a6bad5c14c89b9c945e6df1Bacteria Meet Graphene: Modulation of Graphene Oxide Nanosheet Interaction with Human Pathogens for Effective Antimicrobial TherapyPalmieri, Valentina; Bugli, Francesca; Lauriola, Maria Carmela; Cacaci, Margherita; Torelli, Riccardo; Ciasca, Gabriele; Conti, Claudio; Sanguinetti, Maurizio; Papi, Massimiliano; De Spirito, MarcoACS Biomaterials Science & Engineering (2017), 3 (4), 619-627CODEN: ABSEBA; ISSN:2373-9878. (American Chemical Society)The development of new pharmacol. strategies that evade bacterial resistance became a compelling worldwide challenge. Graphene Oxide (GO) can represent the nanotechnol. answer being economic, easy to produce and to degrade and having multi-target specificity against bacteria. Several groups tried to define the interaction between GO sheets and human pathogens. Unfortunately, controversial results from inhibition to bacterial growth enhancement have been reported. The main difference among all expts. evidences relies on the environmental conditions adopted to study the bacteria-GO interaction. Indeed GO, stable in deionized water, undergoes to a rapid and salt-specific DLVO-like aggregation that influences antimicrobial effects. Considering this phenomenon, interaction of bacteria with GO aggregates having different size, morphol., and surface potential can create a complex scenario that explains the contrasting results reported so far. In this paper, we demonstrate that by modulating the GO stability in soln., the antibacterial or growth enhancement effect can be controlled on Staphylococcus aureus and Escherichia coli. GO at low concn. cut microorganisms membranes and, at high concn., forms complexes with pathogens and inhibits or enhances bacteria growth in a surface potential-dependent manner. With the framework defined in this study the clin. application of GO gets closer and controversial results in literature can be explained.
- 23Guo, Z.; Xie, C.; Zhang, P.; Zhang, J.; Wang, G.; He, X.; Ma, Y.; Zhao, B.; Zhang, Z. Toxicity and Transformation of Graphene Oxide and Reduced Graphene Oxide in Bacteria Biofilm. Sci. Total Environ. 2017, 580, 1300– 1308, DOI: 10.1016/j.scitotenv.2016.12.09323https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XitFehsrbM&md5=b44d5023f1950d0403a463e6b7efdee1Toxicity and transformation of graphene oxide and reduced graphene oxide in bacteria biofilmGuo, Zhiling; Xie, Changjian; Zhang, Peng; Zhang, Junzhe; Wang, Guohua; He, Xiao; Ma, Yuhui; Zhao, Bin; Zhang, ZhiyongScience of the Total Environment (2017), 580 (), 1300-1308CODEN: STENDL; ISSN:0048-9697. (Elsevier B.V.)Impact of graphene based material (GNMs) on bacteria biofilm has not been well understood yet. In this study, the authors compared the impact of graphene oxide (GO) and reduced graphene oxide (rGO) on biofilm formation and development in Luria-Bertani (LB) medium using Escherichia coli and Staphylococcus aureus as models. GO significantly enhanced the cell growth, biofilm formation, and biofilm development even up to a concn. of 500 mg/L. In contrast, rGO (≥50 mg/L) strongly inhibited cell growth and biofilm formation. However, the inhibitory effects of rGO (50 mg/L and 100 mg/L) were attenuated in the mature phase (>24 h) and eliminated at 48 h. GO at 250 mg/L decreased the reactive oxygen species (ROS) levels in biofilm and extracellular region at mature phase. ROS levels were significantly increased by rGO at early phase, while they returned to the same levels as control at mature phase. These results suggest that oxidative stress contributed to the inhibitory effect of rGO on bacterial biofilm. The authors further found that supplement of extracellular polymeric substances (EPS) in the growth medium attenuated the inhibitory effect of rGO on the growth of developed biofilm. XPS results showed that rGO were oxidized to GO which can enhance the bacterial growth. The authors deduced that the elimination of the toxicity of rGO at mature phase was contributed by EPS protection and the oxidn. of rGO. This study provides new insights into the interaction of GNMs with bacteria biofilm.
- 24Papageorgiou, D. G.; Kinloch, I. A.; Young, R. J. Mechanical Properties of Graphene and Graphene-Based Nanocomposites. Prog. Mater. Sci. 2017, 90, 75– 127, DOI: 10.1016/j.pmatsci.2017.07.00424https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtlShur7I&md5=cc409f1fd4839f4540b5823bab880ffcMechanical properties of graphene and graphene-based nanocompositesPapageorgiou, Dimitrios G.; Kinloch, Ian A.; Young, Robert J.Progress in Materials Science (2017), 90 (), 75-127CODEN: PRMSAQ; ISSN:0079-6425. (Elsevier Ltd.)In this present review, the current status of the intrinsic mech. properties of the graphene-family of materials along with the prepn. and properties of bulk graphene-based nanocomposites is thoroughly examd. The usefulness of Raman spectroscopy for the characterization and study of the mech. properties of graphene flakes and their composites is clearly exhibited. Furthermore, the prepn. strategies of bulk graphene-based nanocomposites are discussed and the mech. properties of nanocomposites reported in the literature are analyzed. In particular, through the analyze of several hundred literature papers on graphene composites, we have found a unique correlation between the filler modulus, derived from the rule of mixts., and the composite matrix. This correlation is found to hold true across a wide range of polymer matrixes and thus suggests that the common assumption that the filler modulus is independent of the matric is incorrect, explaining the apparent under performance of graphene in some systems. The presence of graphene even at very low loadings can provide significant reinforcement to the final material, while the parameters that affect the nanocomposite strongly are thoroughly reviewed. Finally, the potential applications and future perspectives are discussed with regard to scale up capabilities and possible developments of graphene-based nanocomposite materials.
- 25Poulin, P.; Jalili, R.; Neri, W.; Nallet, F.; Divoux, T.; Colin, A.; Aboutalebi, S. H.; Wallace, G.; Zakri, C. Superflexibility of Graphene Oxide. Proc. Natl. Acad. Sci. U.S.A. 2016, 113 (40), 11088– 11093, DOI: 10.1073/pnas.160512111325https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsFarsLbP&md5=a6691209062b9dc3c2f5c9b92b443de8Superflexibility of graphene oxidePoulin, Philippe; Jalili, Rouhollah; Neri, Wilfrid; Nallet, Frederic; Divoux, Thibaut; Colin, Annie; Aboutalebi, Seyed Hamed; Wallace, Gordon; Zakri, CecileProceedings of the National Academy of Sciences of the United States of America (2016), 113 (40), 11088-11093CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Graphene oxide (GO), the main precursor of graphene-based materials made by soln. processing, is known to be very stiff. Indeed, it has a Young's modulus comparable to steel, on the order of 300 GPa. Despite its very high stiffness, we show here that GO is superflexible. We quant. measure the GO bending rigidity by characterizing the flattening of thermal undulations in response to shear forces in soln. Characterizations are performed by the combination of synchrotron X-ray diffraction at small angles and in situ rheol. (rheo-SAXS) expts. using the high X-ray flux of a synchrotron source. The bending modulus is 1 kT, which is about two orders of magnitude lower than the bending rigidity of neat graphene. This superflexibility compares with the fluidity of self-assembled liq. bilayers. This behavior is discussed by considering the mechanisms at play in bending and stretching deformations of at. monolayers. The superflexibility of GO is a unique feature to develop bendable electronics after redn., films, coatings, and fibers. This unique combination of properties of GO allows for flexibility in processing and fabrication coupled with a robustness in the fabricated structure.
- 26Kumar, S.; Parekh, S. H. Linking Graphene-Based Material Physicochemical Properties with Molecular Adsorption, Structure and Cell Fate. Commun. Chem. 2020, 3 (1), 8, DOI: 10.1038/s42004-019-0254-926https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXktlynt7c%253D&md5=ec3f7c93c6f874c7a1de9f939f881a91Linking graphene-based material physicochemical properties with molecular adsorption, structure and cell fateKumar, Sachin; Parekh, Sapun H.Communications Chemistry (2020), 3 (1), 8CODEN: CCOHCT; ISSN:2399-3669. (Nature Research)A review. Abstr.: Graphene, an allotrope of carbon, consists of a single layer of carbon atoms with uniquely tuneable properties. As such, graphene-based materials (GBMs) have gained interest for tissue engineering applications. GBMs are often discussed in the context of how different physicochem. properties affect cell physiol., without explicitly considering the impact of adsorbed proteins. Establishing a relationship between graphene properties, adsorbed proteins, and cell response is necessary as these proteins provide the surface upon which cells attach and grow. This review highlights the mol. adsorption of proteins on different GBMs, protein structural changes, and the connection to cellular function.
- 27Wilson, C. J.; Clegg, R. E.; Leavesley, D. I.; Pearcy, M. J. Mediation of Biomaterial–Cell Interactions by Adsorbed Proteins: a Review. Tissue Eng. 2005, 11 (1–2), 1– 18, DOI: 10.1089/ten.2005.11.127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhs12rt7g%253D&md5=e2bdb40542ef8ca45b4762a12e86ca06Mediation of Biomaterial-Cell Interactions by Adsorbed Proteins: A ReviewWilson, Cameron J.; Clegg, Richard E.; Leavesley, David I.; Pearcy, Mark J.Tissue Engineering (2005), 11 (1/2), 1-18CODEN: TIENFP; ISSN:1076-3279. (Mary Ann Liebert, Inc.)A review. An appropriate cellular response to implanted surfaces is essential for tissue regeneration and integration. It is well described that implanted materials are immediately coated with proteins from blood and interstitial fluids, and it is through this adsorbed layer that cells sense foreign surfaces. Hence, it is the adsorbed proteins, rather than the surface itself, to which cells initially respond. Diverse studies using a range of materials have demonstrated the pivotal role of extracellular adhesion proteins-fibronectin and vitronectin in particular-in cell adhesion, morphol., and migration. These events underlie the subsequent responses required for tissue repair, with the nature of cell surface interactions contributing to survival, growth, and differentiation. The pattern in which adhesion proteins and other bioactive mols. adsorb thus elicits cellular reactions specific to the underlying physicochem. properties of the material. Accordingly, in vitro studies generally demonstrate favorable cell responses to charged, hydrophilic surfaces, corresponding to superior adsorption and bioactivity of adhesion proteins. This review illustrates the mediation of cell responses to biomaterials by adsorbed proteins, in the context of osteoblasts and selected materials used in orthopedic implants and bone tissue engineering. It is recognized, however, that the periimplant environment in vivo will differ substantially from the cell-biomaterial interface in vitro. Hence, one of the key issues yet to be resolved is that of the interface compn. actually encountered by osteoblasts within the sequence of inflammation and bone regeneration.
- 28Vacchi, I. A.; Raya, J.; Bianco, A.; Ménard-Moyon, C. Controlled Derivatization of Hydroxyl Groups of Graphene Oxide in Mild Conditions. 2D Materials 2018, 5 (3), 035037, DOI: 10.1088/2053-1583/aac8a928https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXlt1Sjsb8%253D&md5=ffb48c68e472aa82f87bfd8e831ed140Controlled derivatization of hydroxyl groups of graphene oxide in mild conditionsVacchi, Isabella A.; Raya, Jesus; Bianco, Alberto; Menard-Moyon, Cecilia2D Materials (2018), 5 (3), 035037/1-035037/11CODEN: DMATB7; ISSN:2053-1583. (IOP Publishing Ltd.)Graphene oxide (GO) is constituted of various oxygen-contg. functionalities, primarily epoxides and hydroxyl groups on the basal plane, with a very low amt. of carbonyl, quinone, carboxylic acid, phenol, and lactone functions at the edges. The high chem. reactivity of these oxygenated groups makes functionalization difficult to control as different reactions can occur concomitantly. In this study we have investigated the reactivity of GO toward orthogonal reactions to selectively functionalize the hydroxyl groups, which are present in a high amt. We explored both the esterification and the Williamson reaction. Our strategies present the main advantage to occur in mild conditions, thus preserving the intrinsic properties of GO, whereas most reactions reported in literature require relatively harsh conditions, leading to (partial) redn., and/ or are not chemoselective. We have also extended our study to the ketones and examd. their derivatization by the Wittig reaction. This work has allowed developing two facile methods for the covalent derivatization of the hydroxyl groups in mild conditions, while GO was not reactive toward the Wittig reaction, probably due to the low amt. of ketones. Overall, this work leads to a better understanding of the reactivity of GO for controlled derivatization. This opens promising perspectives for multi-functionalization of GO in order to design graphene-based nanomaterials endowed of multiple properties.
- 29Simon-Deckers, A.; Loo, S.; Mayne-L’hermite, M.; Herlin-Boime, N.; Menguy, N.; Reynaud, C.; Gouget, B.; Carriere, M. Size-, Composition-and Shape-Dependent Toxicological Impact of Metal Oxide Nanoparticles and Carbon Nanotubes Toward Bacteria. Environ. Sci. Technol. 2009, 43 (21), 8423– 8429, DOI: 10.1021/es901697529https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXht1artbnJ&md5=4c7537ad2861aaf61ff103cd1a16e7b7Size-, Composition- and Shape-Dependent Toxicological Impact of Metal Oxide Nanoparticles and Carbon Nanotubes toward BacteriaSimon-Deckers, Angelique; Loo, Sylvain; Mayne-L'hermite, Martine; Herlin-Boime, Nathalie; Menguy, Nicolas; Reynaud, Cecile; Gouget, Barbara; Carriere, MarieEnvironmental Science & Technology (2009), 43 (21), 8423-8429CODEN: ESTHAG; ISSN:0013-936X. (American Chemical Society)Ecotoxicol. effects of nanoparticles (NP) are still poorly documented while their commercialization for industrial and household applications increases. The aim of this study was to evaluate the influence of physicochem. characteristics on metal oxide NP and carbon nanotubes toxicol. effects toward bacteria. Two strains of bacteria, Cupriavidus metallidurans CH34 and Escherichia coli MG1655 were exposed to TiO2 or Al2O3 NP or to multiwalled-carbon nanotubes (MWCNT). Particular attention was paid on optimizing NP dispersion to obtain nonagglomerated suspensions. The authors' results show that NP toxicity depends on their chem. compn., size, surface charge, and shape but not on their cryst. phase. MWCNT toxicity does not depend on their purity. Toxicity also depends on the bacterial strain: E. coli MG1655 is sensitive to NP, whereas C. metallidurans CH34 is not. Interestingly, NP are accumulated in both bacterial strains, and assocn. between NP and bacteria is necessary for bacterial death to occur. NP may then represent a danger for the environment, causing the disappearance of some sensitive bacterial strains such as E. coli MG1655, but also being mobilized by nonsensitive strains such as C. metallidurans CH34 and transported through the whole ecosystem.
- 30Faserl, K.; Chetwynd, A. J.; Lynch, I.; Thorn, J. A.; Lindner, H. H. Corona Isolation Method Matters: Capillary Electrophoresis Mass Spectrometry Based Comparison of Protein Corona Compositions Following on-Particle Versus in-Solution or in-Gel Digestion. Nanomaterials 2019, 9 (6), 898, DOI: 10.3390/nano906089830https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsFehtL7L&md5=83b2559836f95e0e4a8da53034605450Corona isolation method matters: capillary electrophoresis mass spectrometry based comparison of protein corona compositions following on-particle versus in-solution or in-gel digestionFaserl, Klaus; Chetwynd, Andrew J.; Lynch, Iseult; Thorn, James A.; Lindner, Herbert H.Nanomaterials (2019), 9 (6), 898CODEN: NANOKO; ISSN:2079-4991. (MDPI AG)Increased understanding of the role of the nanomaterial protein corona in driving nanomaterial uptake into, and impacts on, cells and organisms, and the consequent need for characterization of the corona, has led to a flourishing of methods for isolation and anal. of the constituent proteins over the past decade. However, despite over 700 corona studies to date, very little is understood in terms of which methods provide the most precise and comprehensive characterization of the corona. With the increasing importance of the modeling of corona formation and its correlation with biol. impacts, it is timely to properly characterize and validate the isolation approaches used to det. the protein corona. The current work introduces Capillary Electrophoresis with Electro Spray Ionization Mass Spectrometry (CESI-MS) as a novel method for protein corona characterizations and develops an on-particle tryptic digestion method, comparing peptide solubilization solns. and characterizing the recovery of proteins from the nanomaterial surface. The CESI-MS was compared to the gold std. nano-LC-MS for corona anal. and maintained a high degree of reproducibility, while increasing throughput by >3-fold. These are important factors to consider when designing corona studies and modeling corona formation and impacts, highlighting the significance of a comprehensive validation of nanomaterial corona anal. methods.
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The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.2c10961.
Details materials and methods, survey of the SOC literature of GMs on the antibacterial effects, the characterization of GMs, the antibacterial effects and the potential antibacterial mechanism of GMs, liposome leakage, and MD simulation studies (PDF)
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