A New Mechanism of Model Membrane Fusion Determined from Monte Carlo Simulation

TL;DR

This study uses Monte Carlo simulations to explore a novel membrane fusion pathway involving hole formation and stalk encirclement, differing from the traditional stalk mechanism, and highlights its implications for membrane mixing and leakage.

Contribution

It introduces a new fusion mechanism based on hole nucleation and stalk encirclement, expanding understanding beyond the classical stalk model.

Findings

Fusion involves hole formation and stalk encirclement rather than classical stalk expansion.

Two distinct pathways for membrane fusion were identified.

The process allows for membrane mixing and transient leakage.

Abstract

We have carried out extensive Monte Carlo simulations of the fusion of tense apposed bilayers formed by amphiphilic molecules within the framework of a coarse grained lattice model. The fusion pathway differs from the usual stalk mechanism. Stalks do form between the apposed bilayers, but rather than expand radially to form an axial-symmetric hemifusion diaphragm of the trans leaves of both bilayers, they promote in their vicinity the nucleation of small holes in the bilayers. Two subsequent paths are observed: (i) The stalk encircles a hole in one bilayer creating a diaphragm comprised of both leaves of the other intact bilayer, and which ruptures to complete the fusion pore. (ii) Before the stalk can encircle a hole in one bilayer, a second hole forms in the other bilayer, and the stalk aligns and encircles them both to complete the fusion pore. Both pathways give rise to mixing between the cis and trans leaves of the bilayer and allow for transient leakage.