Lipid Acrobatics in the Membrane Fusion Arena

In this review, we describe the recent contribution of computer simulation approaches to unravel the molecular details of membrane fusion. Over the past decade, fusion between apposed membranes and vesicles has been studied using a large variety of simulation methods and systems. Despite the variety in techniques, some generic fusion pathways emerge that predict a more complex picture beyond the traditional stalk–pore pathway. Indeed the traditional pathway is confirmed in particle-based simulations, but in addition alternative pathways are observed in which stalks expand linearly rather than radially, leading to inverted-micellar or asymmetric hemifusion intermediates. Simulations also suggest that the first barrier to fusion is not the formation of the stalk, but rather, the formation of a lipid bridge consisting of one or two lipids only. Fusion occurring during the fission process involves other intermediates, however, and is not just fusion reversed. Finally, recent progress in simulations of peptide and protein-mediated fusion shows how fusion proceeds in a more biologically relevant scenario.