Ion-Induced Transient Potential Fluctuations Facilitate Pore Formation and Cation Transport through Lipid Membranes
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High Resolution Image Download MS PowerPoint Slide Unassisted ion transport through lipid membranes plays a crucial role in many cell functions without which life would not be possible, yet the precise mechanism behind the process remains unknown due to its molecular complexity. Here, we demonstrate a direct link between membrane potential fluctuations and divalent ion transport. High-throughput wide-field non-resonant second harmonic (SH) microscopy of membrane water shows that membrane potential fluctuations are universally found in lipid bilayer systems. Molecular dynamics simulations reveal that such variations in membrane potential reduce the free energy cost of transient pore formation and increase the ion flux across an open pore. These transient pores can act as conduits for ion transport, which we SH image for a series of divalent cations (Cu 2+, Ca 2+, Ba 2+, Mg 2+ ) passing through giant unilamellar vesicle (GUV) membranes. Combining the experimental and computational results, we show that permeation through pores formed via an ion-induced electrostatic field is a viable mechanism for unassisted ion transport.
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Electropores may form under external electric fields and can also arise spontaneously in naturally occurring systems due to transient transmembrane potentials arising from bilayer-surface charge fluctuations.
“Electropores may form under external electric fields 9 and can also arise spontaneously in naturallyoccuring (particularly biological) systems due to transient transmembrane potentials arising from bilayer-surface charge flucuations 8,12,[22][23][24][25][26][27][28][29][30] .”
From Fusion of lipid membranes: an alternative pathway (2026) · cites this paper as [8]
The Introduction reports that intrinsic membrane-potential fluctuations lower the free energy of transient pores, and the Results and Discussion links those fluctuations to charges in the hydrated lipid-headgroup region. The study examines model membranes and giant unilamellar vesicles; it proposes that such fluctuations are general to lipid membranes but does not establish spontaneous pore formation particularly in biological systems. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe magnitude of these transmembrane potentials is biologically relevant and prevalent in transient states near the surfaces of cell membranes.
“The magnitude of these transmembrane potentials is biologically relevant, prevalent in transient states near the surfaces of cell membranes 8,12 , underscoring the potential importance of this mechanism in biological events.”
From Fusion of lipid membranes: an alternative pathway (2026) · cites this paper as [8]
The Results and Discussion section reports transient potential fluctuations of several hundred millivolts in model lipid membranes and giant unilamellar vesicles, and finds that potentials in this range affect pore formation and ion transport. It proposes that such fluctuations may be a general feature of lipid membranes, but does not establish that they are prevalent near the surfaces of living cell membranes. The biological extension is therefore stronger than the evidence in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThis topologically and energetically distinct pathway for membrane fusion is of particular interest because transmembrane potentials, of similar magnitude to those (ca. 0.1 V/nm) leading to electropores in lipid bilayers, may occur naturally across lipid membranes of vesicles and cells.
“This topologically and energetically distinct pathway for membrane fusion is of particular interest because transmembrane potentials, of similar magnitude to those (ca.0.1V/nm) leading to electropores in lipid bilayers, may occur naturally across lipid membranes of vesicles and cells, as recently demonstrated 8,12 , as well as under external application 9,34 .”
From Fusion of lipid membranes: an alternative pathway (2026) · cites this paper as [8]
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Experimental — accuracy not yet measuredThe enhancement of ΔΦ0 arises from overlapping electric double layers of contact sites, increasing the probability of electroporation preceding the peripore-stalk-zipper pathway.
“This enhancement arises from overlapping electric double layers of contact sites, increasing the probability of electroporation 8,12 preceding the peripore-stalk-zipper pathway.”
From Fusion of lipid membranes: an alternative pathway (2026) · cites this paper as [8]
The Results and Discussion section ('Membrane Potential Fluctuations and Transient Pore Formation'; page unavailable) reports that larger transmembrane potentials stabilize pores, supporting the proposed increase in pore-formation probability. It does not attribute an enhancement of ΔΦ0 to overlapping electric double layers at contact sites or place electroporation before a peripore-stalk-zipper pathway. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAn alternative pathway for membrane fusion arises from electroporation induced by transmembrane potentials in the absence of proteins.
“Here we uncover an alternative pathwaymembrane fusion arising from electroporation induced by transmembrane potentials 8,9 in absence of proteins.”
From Fusion of lipid membranes: an alternative pathway (2026) · cites this paper as [8]
Spontaneous transmembrane potentials arise naturally due to bilayer-surface-charge/electric double layer fluctuations and result in transient membrane electropores.
“As noted, such potentials arise naturally due to bilayer-surface-charge/electric double layer fluctuations, and result in transient membrane electropores 8,12 .”
From Fusion of lipid membranes: an alternative pathway (2026) · cites this paper as [8]
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Cited by
Sorted by citations
Fusion of lipid membranes: an alternative pathway
Jin, D., Li, Z., Roke, S., & Klein, J. (2026) · doi:10.64898/2026.02.19.706911
Self-citation
- Authors
- Roesel, D., Eremchev, M., Poojari, C. S., Hub, J. S., & Roke, S.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Saarland University (DE)
- Corresponding author
- Hub, Jochen S.
- Roke, Sylvie
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2022-12-15
- Volume
- 144
- Issue
- 51
- Pages
- 23352-23357
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC9801421
- OpenAlex
- W4311569790
- Cited by
- 34
- References
- 1
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 9 · 2023: 8
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of the American Chemical Society (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- arXiv (Cornell University)
- Funders
- Schweizerischer Nationalfonds zur F?rderung der Wissenschaftlichen Forschung (200021-182606-1)
- Julia Jacobi Foundation
- Deutsche Forschungsgemeinschaft (SFB 1027/B7)
- H2020 European Research Council (951324)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Physical Sciences › Engineering › Biomedical Engineering › Nanopore and Nanochannel Transport Studies
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Spectroscopy and Quantum Chemical Studies
- Keywords
- membrane potential fluctuations, lipid bilayers, second harmonic generation microscopy, giant unilamellar vesicles, electrostatic field, ion flux
- MeSH terms
- Cations, Lipid Bilayers, Membrane Potentials, Ion Transport, Molecular Dynamics Simulation
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