| dc.description.abstract | Although membrane fusion plays key roles in many biological functions, its underlying molecular mechanism remains poorly understood. We employed all-atom molecular dynamics simulations to investigate the fusion mechanism, catalyzed by Ca2+ ions, of two highly hydrated 1-palmitoyl-2-oleoyl-sn-3-phosphoethanolamine (POPE) micelles and vesicels. Our simulations revealed that Ca2+ ions are capable of catalyzing the fusion of POPE micelles; in contrast, we did not observe close contact of the two micelles in the presence of only Na+ or Mg2+ ions. The Ca2+ ions play a key role in catalyzing the micelle fusion in three aspects: creating a more-hydrophobic surface on the micelles, binding two micelles together, and enhancing the formation of the pre-stalk state. Effective fusion proceeds through sequential formation of pre-stalk, stalk, hemifused-like, and fused states. The pre-stalk state is a state featuring solvent-exposed lipid tails; its formation is the rate-limiting step. The stalk state is a state where a localized hydrophobic core is formed connecting two micelles; its formation occurs in conjunction with a dehydration process between two micelles. Our large-scale simulations of vesicle fusion show the stalk formation is mainly dominated by the outer lipids, but it also involves with the inner lipids. On the other hand, the formation of hemi-fused state is dominated by the inner lipids to a diaphragm. Moreover, more than one stable hemi-fused state can be formed. This study provides insight into the molecular mechanism of membrane fusion from the points of view of energetics, structure, and dynamics. | en_US |