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Cited by 41Lipid Membrane Structure and BehaviorCellular transport and secretionCaveolin-1 and cellular processes

High curvature promotes fusion of lipid membranes: Predictions from continuum elastic theory

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Golani, Gonen, Schwarz, Ulrich S.·2023·Biophysical Journal
DOI 10.1016/j.bpj.2023.04.018PMC PMC10209146
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Abstract

The fusion of lipid membranes progresses through a series of hemifusion intermediates with two significant energy barriers related to the formation of stalk and fusion pore, respectively. These energy barriers determine the speed and success rate of many critical biological processes, including the fusion of highly curved membranes, for example synaptic vesicles and enveloped viruses. Here we use continuum elastic theory of lipid monolayers to determine the relationship between membrane shape and energy barriers to fusion. We find that the stalk formation energy decreases with curvature by up to 31 k B T in a 20-nm-radius vesicle compared with planar membranes and by up to 8 k B T in the fusion of highly curved, long, tubular membranes. In contrast, the fusion pore formation energy barrier shows a more complicated behavior. Immediately after stalk expansion to the hemifusion diaphragm, the fusion pore formation energy barrier is low (15–25 k B T) due to lipid stretching in the distal monolayers and increased tension in highly curved vesicles. Therefore, the opening of the fusion pore is faster. However, these stresses relax over time due to lipid flip-flop from the proximal monolayer, resulting in a larger hemifusion diaphragm and a higher fusion pore formation energy barrier, up to 35 k B T. Therefore, if the fusion pore fails to open before significant lipid flip-flop takes place, the reaction proceeds to an extended hemifusion diaphragm state, which is a dead-end configuration in the fusion process and can be used to prevent viral infections. In contrast, in the fusion of long tubular compartments, the surface tension does not accumulate due to the formation of the diaphragm, and the energy barrier for pore expansion increases with curvature by up to 11 k B T. This suggests that inhibition of polymorphic virus infection could particularly target this feature of the second barrier.

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  • The main mechanism of fusion remains the lipid-mediated topological rearrangements, with proteins largely acting to promote the membrane configurations required for these steps.

    “Yet the main mechanism of fusion remains the lipid-mediated topological rearrangements, with proteins largely acting to promote the membrane configurations required for these steps 19,20 (Fig. 1 A(1)).”

    From Fusion of lipid membranes: an alternative pathway (2026) · cites this paper as [20]

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Authors
Golani, G., & Schwarz, U. S.
Affiliations
Heidelberg University (DE)
Corresponding author
Schwarz, Ulrich S.
ORCID
Venue
Biophysical Journal
Publisher
Elsevier BV
Published
2023-05
Volume
122
Issue
10
Pages
1868-1882
ISSN
0006-3495 (ISSN-L)
DOI
10.1016/j.bpj.2023.04.018
PMC
PMC10209146
OpenAlex
W4366246376
Cited by
41
References
0
Citations by year
2026: 23 · 2025: 11 · 2024: 4 · 2023: 3
FWCI
3.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Biophysical Journal (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Minerva Foundation
  • Deutsche Forschungsgemeinschaft (240245660)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
Keywords
membrane curvature, stalk formation, fusion pore, lipid flip-flop, continuum elastic theory, lipid monolayers, viral infection inhibition, synaptic vesicle fusion, tubular membranes
MeSH terms
Lipid Bilayers, Membrane Fluidity, Membrane Fusion, Membranes, Thermodynamics

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