▎ 摘　　要

Two-dimensional (2D) nanomaterials, such as graphene nanosheets (GNs) and graphene oxide nanosheets (GOs), could adhere onto or insert into a biological membrane, leading to a change in membrane properties and biological activities. Consequently, GN and GO become potential candidates for mediating interleaflet phospholipid transfer. In this work, molecular dynamics (MD) simulations were employed to investigate the effects of GN and GO on lipid flip-flop behavior and the underlying molecular mechanisms. Of great interest is that GN and GO work in opposite directions. The inserted GN can induce the formation of an ordered nanodomain, which dramatically elevates the free energy barrier of flipping phospholipids from one leaflet to the other, thus leading to a decreased lipid flip-flop rate. In contrast, the embedded GO can catalyze the transport of phospholipids between membrane leaflets by facilitating the formation of water pores. These results suggest that GN may work as an inhibitor of the interleaflet lipid translocation, while GO may play the role of scramblases. These findings are expected to expand promising biomedical applications of 2D nanomaterials. (c) 2023 Elsevier Inc. All rights reserved.