(770f) ­­­Influence of Single-Stranded DNA Coatings on the Interaction between Graphene Nanoflakes and Lipid Bilayers

Graphene and related materials have shown considerable promise in biomedical applications, such as graphene-based electrodes for use in the examination of neuronal networks (1). However, bringing graphene in close proximity to cells or tissues can be problematic since graphene is reportedly cytotoxic (2). Computational studies have demonstrated the spontaneous insertion of graphene nanoflakes (GNFs) into lipid membranes (3). Other studies have demonstrated significant membrane disruption resulting from the extraction of lipids from the membrane by a partially inserted GNF (4). These behaviors have been associated with the hydrophobicity of the GNF, whereby insertion and extraction of lipids occurs to shield the GNF from the surrounding water. As such, coating GNFs to reduce the hydrophobicity, is one potential route to mitigate the disruptive and cytotoxic behavior.

Here, using molecular dynamics simulations, we examine the interactions and insertion behavior of both bare and coated GNFs. It is demonstrated that a partial coating of single-stranded DNA (ssDNA) reduces the penetration depth of a GNF into a phospholipid/cholesterol bilayer by attenuating the hydrophobic force that drives the penetration. As the GNF penetrates the bilayer, the DNA remains adsorbed to the GNF outside of the bilayer, where it shields the graphene from the surrounding water, preventing any significant lipid extraction or membrane disruption. The penetration depth is found to be controlled by the amount of ssDNA coating the GNF, with a sparser coating resulting in a deeper penetration since the ssDNA shields less of the GNF surface. As the coating density is increased, the likelihood of the GNF entering the bilayer is also reduced, where it instead lies flat on the bilayer surface with the sugar phosphate backbone of ssDNA interacting with the hydrophilic lipid headgroups and water. As such, a coating of ssDNA may reduce the cytotoxicity of GNFs by shielding the unfavorable graphene-water interaction, reducing or even preventing graphene penetration and lipid bilayer disruption.

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2. Zhang, Y., Ali, S.F., Dervishi, E., Xu, Y., Li, Z., Casciano, D. and Biris, A.S., 2010. Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells. ACS nano, 4(6), pp.3181-3186.
3. Li, Y., Yuan, H., Von Dem Bussche, A., Creighton, M., Hurt, R.H., Kane, A.B. and Gao, H., 2013. Graphene microsheets enter cells through spontaneous membrane penetration at edge asperities and corner sites. Proceedings of the National Academy of Sciences, 110(30), pp.12295-12300.
4. Tu, Y., Lv, M., Xiu, P., Huynh, T., Zhang, M., Castelli, M., Liu, Z., Huang, Q., Fan, C., Fang, H. and Zhou, R., 2013. Destructive extraction of phospholipids from Escherichia coli membranes by graphene nanosheets. Nature nanotechnology, 8(8), p.594.