Pathways for fast and slow fusion of nanovesicles without membrane rupture

Eukaryotic cells continuously remodel their membrane architecture by fusion processes, which are initiated by the adhesion of two membranes and eventually lead to a single membrane with a membrane neck or fusion pore. The fusion of cellular membranes involves membrane proteins but the fusion of biomimetic membranes such as lipid bilayers can be induced by bilayer tension even in the absence of proteins. Tension-induced fusion competes however with membrane rupture, which tends to impair the fusion process. Here, we show by molecular dynamics simulations that nanovesicles enclosed by tensionless and asymmetric bilayers can undergo fusion without rupture and that these fusion processes follow two distinct pathways, a slow and a fast one. Fast fusion starts immediately after an initial point contact between the two vesicles has been established whereas slow fusion occurs only after the vesicles have formed a spatially extended contact area. The two pathways are controlled by the stress asymmetry between the two bilayer leaflets or, equivalently, by the resulting transbilayer torque. Our simulation results have important consequences for the free energy landscapes corresponding to fast and slow fusion of nanovesicles, for experimental studies elucidating these fusion pathways, and for protein-mediated fusion of cellular membranes.