Metastable hemifusion diaphragms regulate rim-pore expansion dynamics.

Area of Science:

• Biophysics
• Computational Biology
• Membrane Dynamics

Background:

• Membrane fusion is a critical biological process involving intermediate structures called hemifusion diaphragms.
• The disassembly of these diaphragms under confinement can occur via distinct radial or lateral expansion modes.
• The preferred disassembly pathway is influenced by diaphragm size and the energetic costs of lipid reabsorption.

Purpose of the Study:

• To develop a theoretical model explaining the size-dependent disassembly mechanisms of confined hemifusion diaphragms.
• To elucidate the role of constrained-wetting physics in dictating lateral versus radial rim-pore propagation.
• To understand the implications for controlled membrane self-reorganization.

Main Methods:

• Coarse-grained unbiased molecular dynamics simulations of confined vesicle-in-vesicle systems (μs-scale).
• Development of an analytical geometrical model based on interface wetting and line tensions.
• Inclusion of lipid reabsorption terms accounting for area transfer and stress asymmetry.
• Quantitative comparison of simulation observables (rim-pore area, lengths, contact angles) with model predictions.

Main Results:

• A wetting-inspired energy model predicts two distinct disassembly regimes based on hemifusion diaphragm size.
• Large diaphragms favor lateral propagation, minimizing edge length and reabsorption costs, leading to rapid expansion and fission.
• Small diaphragms favor radial propagation, resulting in slow bleb reabsorption without fragment excision.
• Molecular dynamics simulations quantitatively validated these predictions across multiple replicas.

Conclusions:

• The study unifies geometric and wetting analogies with simulation evidence to reveal a mechanistic pathway for hemifusion diaphragm disassembly.
• The findings demonstrate size-dependent selective fast (lateral) or slow (radial) disassembly under spatial confinement.
• This provides insights into controlled membrane self-reorganization processes.