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Point-Like Protrusion as a Prestalk Intermediate in Membrane Fusion Pathway

Avishay Efrat ^* , Leonid V. Chernomordik  and Michael M. Kozlov ^*

^* Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Faculty of Sciences, Holon Institute of Technology, Holon, Israel; and Section on Membrane Biology, Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland

Correspondence: Address reprint requests and inquiries to Michael M. Kozlov, E-mail: michk{at}post.tau.ac.il.

The widely accepted pathway of membrane fusion begins with the fusion stalk representing the initial intermediate of hemifusion. The lipid structures preceding hemifusion and their possible influence on fusion kinetics were not addressed. Here, we suggest the point-like protrusion as a prestalk fusion intermediate, which has energy lower than that of stalk and, therefore, does not limit the fusion rate. We demonstrate that by calculating the energy of the point-like protrusion, which depends on the lipid monolayer elastic parameters and the strength of the intermembrane hydration repulsion. The point-like protrusion completes the fusion-through-hemifusion model of membrane merger.

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