Curvature-driven lipid sorting: coarse-grained dynamics simulations of a membrane mimicking a hemifusion intermediate

Abstract

How membrane curvature influences lipid dis- tribution is under intensive research. In this short report, after a brief review of recent stud- ies, the results of our coarse-grained (CG) mo- lecular dynamics simulations of membranes with “hemifused ribbons” geometry are dis- cussed. When membranes of a binary mixture of (dipalmitoyl-phosphatidylcholine (DPPC) / diol- eoyl-phosphatidylethanolamine (DOPE) were used, DOPE accumulated in the negatively curved region of the monolayer that formed as the proximal monolayers fused (i.e., cis leaflets). However, the enrichment was dependent on the presence of tethering molecules which kept the curvature high (the curvature radius of ~1 nm), placing the cis monolayers ~2-2.5 nm from each other. Simulations in which DOPE was replaced with dioleoyl-phosphatidylcholine (DOPC) sh- owed an insignificant degree of DOPC accumu- lation, suggesting the importance of lateral in- teraction among DOPE molecules for the cur- vature sorting. The above composition was not close to a demixing point and our radial distri- bution function analysis suggested that the DOPE accumulation was not assisted by the lipid phase separation which has been shown to promote curvature-driven lipid sorting. Rele- vance of curvature-driven lipid sorting to bio- logical membrane fusion is discussed. Keywords: Membrane Fusion; Raft; Mem