Interaction of graphene oxide with artificial cell membranes: Role of anionic phospholipid and cholesterol in nanoparticle attachment and membrane disruption

Abstract A mechanistic understanding of the interaction of graphene oxide (GO) with cell membranes is critical for predicting the biological effects of GO following accidental exposure and biomedical applications. We herein used a quartz crystal microbalance with dissipation monitoring (QCM-D) to probe the interaction of GO with model cell membranes modified with anionic lipids or cholesterol under biologically relevant conditions. The attachment efficiency of GO on supported lipid bilayers (SLBs) decreased with increasing anionic lipid content and was unchanged with varying cholesterol content. In addition, the incorporation of anionic lipids to the SLBs renders the attachment of GO partially reversible upon a decrease in solution ionic strength. These results demonstrate the critical role of lipid bilayer surface charge in controlling GO attachment and release. We also employed the fluorescent dye leakage technique to quantify the role of anionic lipids and cholesterol in vesicle disruption caused by GO. Notably, we observed a linear correlation between the amount of dye leakage from the vesicles and the attachment efficiencies of GO on the SLBs, confirming that membrane disruption is preceded by GO attachment. This study highlights the non-negligible roles of lipid bilayer composition in controlling the physicochemical interactions between cell membranes and GO.