ArticleBiophysical journal2023
A hemifused complex is the hub in a network of pathways to membrane fusion.
Article in Biophysical journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- Using multiscale molecular dynamics simulations to explore the fusion machinery underlying neurotransmitter release.Quarterly reviews of biophysics · 2025Review
- Hemifusomes and interacting proteolipid nanodroplets mediate multi-vesicular body formation.Nature communications · 2025Article
- Hemifusomes and Interacting Proteolipid Nanodroplets Mediate Multi-Vesicular Body Formation.Research square · 2024Article
- Three membrane fusion pore families determine the pathway to pore dilation.Biophysical journal · 2023Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Membrane fusion is a critical step for many essential processes, from neurotransmission to fertilization. For over 40 years, protein-free fusion driven by calcium or other cationic species has provided a simplified model of biological fusion, but the mechanisms remain poorly understood. Cation-mediated membrane fusion and permeation are essential in their own right to drug delivery strategies based on cell-penetrating peptides or cation-bearing lipid nanoparticles. Experimental studies suggest calcium drives anionic membranes to a hemifused intermediate that constitutes a hub in a network of pathways, but the pathway selection mechanism is unknown. Here we develop a mathematical model that identifies the network hub as a highly dynamic hemifusion complex. Multivalent cations drive expansion of this high-tension hemifusion interface between interacting vesicles during a brief transient. The fate of this interface determines the outcome, either fusion, dead-end hemifusion, or vesicle lysis. The model reproduces the unexplained finding that calcium-driven fusion of vesicles with planar membranes typically stalls at hemifusion, and we show the equilibrated hemifused state is a novel lens-shaped complex. Thus, membrane fusion kinetics follow a stochastic trajectory within a network of pathways, with outcome weightings set by a hemifused complex intermediate.
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Registered trials
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