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Metastable hemifusion diaphragms regulate rim-pore expansion dynamics.

Luis S Mayorga1, Diego Masone2

  • 1Instituto de Histología y Embriología de Mendoza (IHEM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET),Universidad Nacional de Cuyo (UNCuyo), Mendoza, 5500, Argentina; Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo (UNCuyo), Mendoza, 5500, Argentina.

Journal of Colloid and Interface Science
|May 30, 2026
PubMed
Summary
This summary is machine-generated.

Large hemifusion diaphragms favor lateral expansion, while small ones prefer radial growth. This difference in membrane fusion disassembly is explained by a new wetting-inspired model considering lipid reabsorption costs.

Keywords:
BolalipidsConfinementExpansionHemifusion diaphragmRim pore

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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.