ArticleProceedings of the National Academy of Sciences of the United States of America2019
Thermodynamically reversible paths of the first fusion intermediate reveal an important role for membrane anchors of fusion proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 90 citations in OpenAlex.
- Let's Stalk about Membranes: Committor-Based Enhanced Sampling of Stalk Formation.The journal of physical chemistry letters · 2026Article
- Lipid Disorder and PIP2-Regulated Clustering of Syntaxin-1 JMD-TMD Regions Govern Membrane Fusion Competence.International journal of molecular sciences · 2026Article
- C-Terminal Nucleobase Modification Amplifies Peptide-Mediated Liposome Fusion.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Conformational Flexibility of Transmembrane Helices: How it Works and Where it Matters.Chemical reviews · 2026Review
- Transmembrane domains of fusion proteins promote stalk formation by inducing membrane disorder.Biophysical journal · 2026Article
- Dynamic nanoscale architecture of synaptic vesicle fusion in mouse hippocampal neurons.Nature communications · 2025Article
- Using multiscale molecular dynamics simulations to explore the fusion machinery underlying neurotransmitter release.Quarterly reviews of biophysics · 2025Review
- How SNARE proteins generate force to fuse membranes.Biophysical journal · 2025Article
- Boosting Lipofection Efficiency Through Enhanced Membrane Fusion Mechanisms.International journal of molecular sciences · 2024Review
- Cell-inspired, massive electromodulation of friction via transmembrane fields across lipid bilayers.Nature materials · 2024Article
- Fission of double-membrane tubes under tension.Biophysical journal · 2024Article
- Visualizing intermediate stages of viral membrane fusion by cryo-electron tomography.Trends in biochemical sciences · 2024Review
- The diffuse interface description of fluid lipid membranes captures key features of the hemifusion pathway and lateral stress profile.PNAS nexus · 2024Article
- Novel non-helical antimicrobial peptides insert into and fuse lipid model membranes.Soft matter · 2024Article
- Mechanisms of SNARE proteins in membrane fusion.Nature reviews. Molecular cell biology · 2024Review
- The local variation of the Gaussian modulus enables different pathways for fluid lipid vesicle fusion.Scientific reports · 2024Article
- Article
- High curvature promotes fusion of lipid membranes: Predictions from continuum elastic theory.Biophysical journal · 2023Article
- Two modes of fusogenic action for influenza virus fusion peptide.PLoS computational biology · 2023Article
- Tuning the Extracellular Vesicles Membrane through Fusion for Biomedical Applications.Journal of functional biomaterials · 2023Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biological membrane fusion proceeds via an essential topological transition of the two membranes involved. Known players such as certain lipid species and fusion proteins are generally believed to alter the free energy and thus the rate of the fusion reaction. Quantifying these effects by theory poses a major challenge since the essential reaction intermediates are collective, diffusive and of a molecular length scale. We conducted molecular dynamics simulations in conjunction with a state-of-the-art string method to resolve the minimum free-energy path of the first fusion intermediate state, the so-called stalk. We demonstrate that the isolated transmembrane domains (TMDs) of fusion proteins such as SNARE molecules drastically lower the free energy of both the stalk barrier and metastable stalk, which is not trivially explained by molecular shape arguments. We relate this effect to the local thinning of the membrane (negative hydrophobic mismatch) imposed by the TMDs which favors the nearby presence of the highly bent stalk structure or prestalk dimple. The distance between the membranes is the most crucial determinant of the free energy of the stalk, whereas the free-energy barrier changes only slightly. Surprisingly, fusion enhancing lipids, i.e., lipids with a negative spontaneous curvature, such as PE lipids have little effect on the free energy of the stalk barrier, likely because of its single molecular nature. In contrast, the lipid shape plays a crucial role in overcoming the hydration repulsion between two membranes and thus rather lowers the total work required to form a stalk.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.