Field Theoretic Study of Bilayer Membrane Fusion: II. Mechanism of a Stalk-Hole Complex

TL;DR

This study uses self-consistent field theory to analyze an alternative membrane fusion mechanism involving non-axial stalk expansion, revealing a lower energy barrier and explaining transient leakage phenomena observed experimentally.

Contribution

It introduces a new membrane fusion pathway involving stalk-hole complexes and compares its energetic profile to the standard mechanism, showing its viability.

Findings

The alternative mechanism has a lower fusion barrier by a few k_BT.

Transient leakage varies with system architecture and tension.

The stalk-hole complex facilitates membrane destabilization.

Abstract

We use self-consistent field theory to determine structural and energetic properties of intermediates and transition states involved in bilayer membrane fusion. In particular, we extend our original calculations from those of the standard hemifusion mechanism, which was studied in detail in the first paper of this series, to consider a possible alternative to it. This mechanism involves non-axial stalk expansion, in contrast to the axially symmetric evolution postulated in the classical mechanism. Elongation of the initial stalk facilitates the nucleation of holes and leads to destabilization of the fusing membranes via the formation of a stalk-hole complex. We study properties of this complex in detail, and show how transient leakage during fusion, previously predicted and recently observed in experiment, should vary with system architecture and tension. We also show that the barrier to fusion in the alternative mechanism is lower than that of the standard mechanism by a few $k_BT$ over most of the relevant region of system parameters, so that this alternative mechanism is a viable alternative to the standard pathway.