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Lipid Phase Influences the Dynamic Interactions between Graphene Oxide Nanosheets and a Phospholipid Membrane.

To understand the possible perturbations of graphene oxide (GO) nanosheets on cell membranes is the first step to evaluate their cytotoxicity, while the membrane heterogeneity such like lipid phase separation complicates such interactions. Using the dynamic giant unilamellar vesicle leakage assays, atomic force microscopy characterizations, and molecular dynamics simulations, we demonstrated the structural and property disturbance of GO on a lipid bilayer membrane in a low ionic strength and neutral pH condition, specifically the influence of lipid phase on this process. GO tends to obliquely insert into and even be sandwiched between leaflets of a liquid-phase membrane, inducing formidable flaw in lipid packing states and fast transmembrane leakage. However, GO adopts parallel adsorption or vertical insertion on/into a gel-phase bilayer, while permeabilization occurs only when the disturbance is strong enough. Our results are helpful to understand the fundamental interaction mechanism between GO nanosheets and cells.