Understanding how nanomaterials interact with cell membranes is related to how they cause cytotoxicity and is therefore critical for designing safer biomedical applications. Recently, graphene (a two-dimensional nanomaterial) was shown to have antibacterial activity on Escherichia coli, but its underlying molecular mechanisms remain unknown. Here we show experimentally and theoretically that pristine graphene and graphene oxide nanosheets can induce the degradation of the inner and outer cell membranes of Escherichia coli, and reduce their viability. Transmission electron microscopy shows three rough stages, and molecular dynamics simulations reveal the atomic details of the process. Graphene nanosheets can penetrate into and extract large amounts of phospholipids from the cell membranes because of the strong dispersion interactions between graphene and lipid molecules. This destructive extraction offers a novel mechanism for the molecular basis of graphene's cytotoxicity and antibacterial activity.
At a glance
- Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science 312, 1027–1030 (2006). et al.
- Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307, 538–544 (2005). et al.
- Nanotechnology in cancer medicine. Phys. Today 65, 38–42 (August, 2012). &
- Understanding biophysicochemical interactions at the nano–bio interface. Nature Mater. 8, 543–557 (2009). et al.
- Nanotoxicology: are carbon nanotubes safe? Nature Nanotech. 3, 191–192 (2008). , &
- Toxic potential of materials at the nanolevel. Science 311, 622–627 (2006). , , &
- Molecular mechanism of pancreatic tumor metastasis inhibition by Gd@C82(OH)22 and its implication for de novo design of nanomedicine. Proc. Natl Acad. Sci. USA 109, 15431–15436 (2012). et al.
- Binding of blood proteins to carbon nanotubes reduces cytotoxicity. Proc. Natl Acad. Sci. USA 108, 16968–16973 (2011). et al.
- Computer simulation study of fullerene translocation through lipid membranes. Nature Nanotech. 3, 363–368 (2008). et al.
- Translocation of C60 and its derivatives across a lipid bilayer. Nano Lett. 7, 614–619 (2007). , , , &
- Cell entry of one-dimensional nanomaterials occurs by tip recognition and rotation. Nature Nanotech. 6, 714–719 (2011). , , , &
- Blocking of carbon nanotube based nanoinjectors by lipids: a simulation study. Nano Lett. 8, 2751–2756 (2008). &
- Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural Phaeochromocytoma-derived PC12 cells. ACS Nano 4, 3181–3186 (2010). et al.
- Computer simulation of the translocation of nanoparticles with different shapes across a lipid bilayer. Nature Nanotech. 5, 579–583 (2010). &
- Receptor-mediated endocytosis of nanoparticles of various shapes. Nano Lett. 11, 5391–5395 (2011). , &
- Graphene: status and prospects. Science 324, 1530–1534 (2009).
- Graphene in biomedicine: opportunities and challenges. Nanomedicine 6, 317–324 (2011). &
- Biological interactions of graphene-family nanomaterials: an interdisciplinary review. Chem. Res. Toxicol. 25, 15–34 (2011). , , &
- PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J. Am. Chem. Soc. 130, 10876–10877 (2008). , , &
- Beyond foreign-body-induced carcinogenesis: impact of reactive oxygen species derived from inflammatory cells in tumorigenic conversion and tumor progression. Int. J. Cancer 121, 2364–2372 (2007).
- Production, properties and potential of graphene. Carbon 48, 2127–2150 (2010). , &
- Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett. 10, 3318–3323 (2010). et al.
- Graphene-based antibacterial paper. ACS Nano 4, 4317–4323 (2010). et al.
- Toxicity of graphene and graphene oxide nanowalls against bacteria. ACS Nano 4, 5731–5736 (2010). &
- Antibacterial activity of graphite, graphite oxide, graphene oxide, and reduced graphene oxide: membrane and oxidative stress. ACS Nano 5, 6971–6980 (2011). et al.
- Antibacterial efficiency of graphene nanosheets against pathogenic bacteria via lipid peroxidation. J. Phys. Chem. C 116, 17280–17287 (2012). , , , &
- Protein corona-mediated mitigation of cytotoxicity of graphene oxide. ACS Nano 5, 3693–3700 (2011). et al.
- Preparation of graphitic oxide. J. Am. Chem. Soc. 80, 1339–1339 (1958). &
- Mechanisms of endocytosis. Annu. Rev. Biochem. 78, 857–902 (2009). &
- Nanoparticle-mediated cellular response is size-dependent. Nature Nanotech. 3, 145–150 (2008). , , &
- Observation of a dewetting transition in the collapse of the melittin tetramer. Nature 437, 159–162 (2005). , , &
- Hydrophobic collapse in multidomain protein folding. Science 305, 1605–1609 (2004). , , &
- Dewetting and hydrophobic interaction in physical and biological systems. Annu. Rev. Phys. Chem. 60, 85–103 (2009). , &
- Lateral dimension-dependent antibacterial activity of graphene oxide sheets. Langmuir 28, 12364–12372 (2012). et al.
- Structure of graphite oxide revisited. J. Phys. Chem. B 102, 4477–4482 (1998). , , &
- Understanding the pH-dependent behavior of graphene oxide aqueous solutions: a comparative experimental and molecular dynamics simulation study. Langmuir 28, 235–241 (2012). , , , &
- Hydrogen bond networks in graphene oxide composite paper: structure and mechanical properties. ACS Nano 4, 2300–2306 (2010). , , &
- Atomic structure of reduced graphene oxide. Nano Lett. 10, 1144–1148 (2010). et al.
- Probing the thermal deoxygenation of graphene oxide using high-resolution in situ X-ray-based spectroscopies. J. Phys. Chem. C 115, 17009–17019 (2011). , , &
- Longitudinal unzipping of carbon nanotubes to form graphene nanoribbons. Nature 458, 872–876 (2009). et al.
- Graphene oxide-based antibacterial cotton fabrics. Adv. Healthcare Mater. (in the press). et al.
- Molecular basis for membrane phospholipid diversity: why are there so many lipids? Annu. Rev. Biochem. 66, 199–232 (1997).
- A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom. Nature 430, 232–235 (2004). &
- Phosphatidylethanolamine–phosphatidylglycerol bilayer as a model of the inner bacterial membrane. Biophys. J. 88, 1091–1103 (2005). , &
- Role of phosphatidylglycerols in the stability of bacterial membranes. Biochimie 90, 930–938 (2008). , , , &
- Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys. J. 72, 2002–2013 (1997). , &
- Methodological issues in lipid bilayer simulations. J. Phys. Chem. B 107, 9424–9433 (2003). , , , &
- Experimental validation of molecular dynamics simulations of lipid bilayers: a new approach. Biophys. J. 88, 805–817 (2005). , , &
- Synthesis and solid-state NMR structural characterization of 13C-labeled graphite oxide. Science 321, 1815–1817 (2008). et al.