Tension-induced vesicle fusion: pathways and pore dynamics

Abstract

The dynamics of tension-induced fusion of two vesicles is studied using dissipative particle dynamics (DPD) simulations. The vesicle membranes use an improved DPD parameter set that results in their sustaining only a 10-30% relative area stretch before rupturing on the microsecond timescale of the simulations. Two distinct fusion pathways are observed depending on the initial vesicle tensions. In pathway I, at low membrane tension, a flattened adhesion zone is formed between the vesicles, and one vesicle subsequently ruptures in this contact zone to form a hemifusion state. This state is unstable and eventually opens a pore to complete the fusion process. In pathway II, at higher tension, a stalk is formed during the fusion process that is then transformed by transmembrane pore formation into a fusion pore. Whereas the latter pathway II resembles stalk pathways as observed in other simulation studies, fusion pathway I, which does not involve any stalk formation, has not been described previously to the best of our knowledge. A statistical analysis of the various processes shows that fusion is the dominant pathway for releasing the tension of the vesicles. The functional dependence of the observed fusion time on membrane tension implies that the fusion process is completed by overcoming two energy barriers with scales of 13kBT and 11kBT. The fusion pore radius as a function of time has also been extracted from the simulations, and provides a quantitative measure of the fusion dynamics which are in agreement with recent experiments.