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Cited by 47Lipid Membrane Structure and BehaviorProtein Structure and DynamicsLipid metabolism and biosynthesis

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Molecular mechanisms of spontaneous curvature and softening in complex lipid bilayer mixtures

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Lessen, Henry J., Sapp, Kayla C., Beaven, Andrew H., Ashkar, Rana, Sodt, Alexander J.·2022·Biophysical Journal
DOI 10.1016/j.bpj.2022.07.036PMC PMC9463698

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Abstract

Membrane reshaping is an essential biological process. The chemical composition of lipid membranes determines their mechanical properties and thus the energetics of their shape. Hundreds of distinct lipid species make up native bilayers, and this diversity complicates efforts to uncover what compositional factors drive membrane stability in cells. Simplifying assumptions, therefore, are used to generate quantitative predictions of bilayer dynamics based on lipid composition. One assumption commonly used is that "per lipid" mechanical properties are both additive and constant-that they are an intrinsic property of lipids independent of the surrounding composition. Related to this is the assumption that lipid bulkiness, or "shape," determines its curvature preference, independently of context. In this study, all-atom molecular dynamics simulations on three separate multilipid systems were used to explicitly test these assumptions, applying methodology recently developed to isolate properties of single lipids or nanometer-scale patches of lipids. The curvature preference experienced by populations of lipid conformations were inferred from their redistribution on a dynamically fluctuating bilayer. Representative populations were extracted by both structural similarity and semi-automated hidden Markov model analysis. The curvature preferences of lipid dimers were then determined and compared with an additive model that combines the monomer curvature preference of both the individual lipids. In all three systems, we identified conformational subpopulations of lipid dimers that showed non-additive curvature preference, in each case mediated by a special chemical interaction (e.g., hydrogen bonding). Our study highlights the importance of specific chemical interactions between lipids in multicomponent bilayers and the impact of interactions on bilayer stiffness. We identify two mechanisms of bilayer softening: diffusional softening, driven by the dynamic coupling between lipid distributions and membrane undulations, and conformational softening, driven by the inter-conversion between distinct dimeric conformations.

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Metadata

Authors
Lessen, H. J., Sapp, K. C., Beaven, A. H., Ashkar, R., & Sodt, A. J.
Affiliations
  • National Institutes of Health (US)
  • Virginia Tech (US)
Corresponding author
Sodt, Alexander J.
ORCID
Venue
Biophysical Journal
Publisher
Elsevier BV
Published
2022-09
Volume
121
Issue
17
Pages
3188-3199
ISSN
0006-3495 (ISSN-L)
DOI
10.1016/j.bpj.2022.07.036
PMC
PMC9463698
OpenAlex
W4289732201
Cited by
47
References
4
Citations by year
2026: 15 · 2025: 12 · 2024: 9 · 2023: 8 · 2022: 3
FWCI
2.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Biophysical Journal (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of General Medical Sciences (1Fi2GM137844-01)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development
  • National Science Foundation (MCB-2137154)
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
spontaneous curvature, membrane undulation, lipid composition
MeSH terms
Hydrogen Bonding, Lipid Bilayers, Molecular Conformation, Molecular Dynamics Simulation

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CoChat. (2026). Citation check: Molecular mechanisms of spontaneous curvature and softening in complex lipid bilayer mixtures. https://app.cochat.ai/papers/10.1016/j.bpj.2022.07.036
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Lessen, H. J., Sapp, K. C., Beaven, A. H., Ashkar, R., & Sodt, A. J. (2022). Molecular mechanisms of spontaneous curvature and softening in complex lipid bilayer mixtures. Biophysical Journal. https://doi.org/10.1016/j.bpj.2022.07.036