Molecular Insights into the Membrane Phase Separation Influenced by Membrane/Lipid Structural Changes

doi:10.1007/s40242-025-5083-z

Abstract

Abstract: Cell membranes exhibit complex phase behaviors governed by intricate lipid-lipid interactions, which play pivotal roles in cellular processes, such as signaling and membrane trafficking. However, the molecular mechanisms underlying these phenomena, particularly their associations of lipid structural modifications (e.g., peroxidation) and membrane architecture (monolayer vs. bilayer), remain poorly understood. Here, we employ coarse-grained molecular dynamics simulations to systematically investigate the influence of membrane and lipid structure on phase separation. Our simulations found that monolayers exhibit stronger phase separation and higher lipid ordering than bilayers, underscoring the regulatory role of trans-bilayer coupling. Furthermore, we also found that even minor lipid structural modifications induced by peroxidation are able to enhance phase separation through three distinct mechanisms: increased lipid area, reduced diffusion coefficients, and altered cholesterol orientation. These findings provide molecular-level insights into the interplay among membrane architecture, lipid structure, and phase behavior, with potential implications for biomedical applications.

Key words: Molecular dynamics simulation, Lipid, Cell membrane, Phase separation

NIU Jingjing, DONG Xuewei, PAN Wenyan, YUAN Bing, YANG Kai. Molecular Insights into the Membrane Phase Separation Influenced by Membrane/Lipid Structural Changes[J]. Chemical Research in Chinese Universities, 2026, 42(1): 244-250.

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