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

How membrane curvature influences lipid distribution is under intensive research. In this short report, after a brief review of recent studies, the results of our coarse-grained (CG) molecular dynamics simulations of membranes with “hemifused ribbons” geometry are discussed. When membranes of a binary mixture of (dipalmitoyl-phosphatidylcholine (DPPC) / dioleoyl-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) showed an insignificant degree of DOPC accumulation, suggesting the importance of lateral interaction among DOPE molecules for the curvature sorting. The above composition was not close to a demixing point and our radial distribution 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. Relevance of curvature-driven lipid sorting to biological membrane fusion is discussed.