Insights into the molecular mechanism of membrane fusion from simulation: evidence for the association of splayed tails.

We present coarse-grained simulations of fusion between two liposomes from which a detailed picture of lipid movements emerges. In these simulations the bilayers dilate at the contact edge, and the resulting increase in the area per lipid produces a tilting of the individual molecules as predicted. Fusion is initiated when some of these tilted lipids splay their aliphatic tails, such that the molecules are shared between the opposing leaflets. Multiple splayed lipids subsequently associate with their aliphatic tails in contact, which produces a new hydrophobic core. As the tails extend into a more parallel conformation the two outer leaflets become contiguous to produce a hemifused structure. The results have interesting implications for biological membrane fusion and suggest new possibilities for designing molecules that control fusion.