The Mechanism of Vesicle Fusion as Revealed by Molecular Dynamics Simulations

We describe molecular dynamics simulations elucidating the molecular details of the process of fusion for small lipid vesicles. The simulations are based on a coarse grained (CG) lipid model that accurately represents the lamellar state of a variety of phospholipids and enables us to observe intermediate stages during fusion at near atomic detail. Simulations were conducted on a variety of systems containing common phospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysoPC, and mixtures of the above. The fusion intermediates found are in general agreement with the stalk-pore mechanism. Transient pores sometimes form adjacent to the stalk, however, resulting in the mixing of lipids from the outer and inner monolayers. The speed of stalk formation and the opening of the fusion pore can be modulated by altering the lipid composition in qualitative agreement with experimental observations.