Bending the rules: Molecular dynamics of hydroxylated sphingolipid membranes with 2-hydroxyoleic acid

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids Pub Date : 2025-02-11 DOI:10.1016/j.chemphyslip.2025.105475

Lucia Sessa , Simona Concilio , Miriam Di Martino , Davide Romanini , Xavier Busquets , Stefano Piotto

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引用次数: 0

Abstract

In this study, we introduce a novel method for quantifying the mechanical properties of lipid membranes-bending rigidity (κ), Gaussian rigidity (κ_G), and surface tension (γ) using molecular dynamics (MD) simulations. Our approach is applied to membranes incorporating 2-hydroxyoleic acid (2OHOA), a synthetic oleic acid derivative currently under clinical investigation for its anticancer properties. 2OHOA modifies the plasma membrane composition in cancer cells and activates sphingomyelin synthase 1 (SMS1), an enzyme critical for maintaining sphingolipid levels in the plasma membrane. This research focuses on how the integration of 2OHOA into ceramide and sphingomyelin alters the mechanical and biophysical properties of these membranes. We employed MD simulations to analyze structural parameters such as lipid area, volume, and bilayer thickness. Additionally, by constructing a system of linear equations based on the Helfrich-Seifert model, we estimated the mechanical properties of hydroxylated versus non-hydroxylated membranes. Our findings reveal significant membrane rigidity and curvature changes due to hydroxylation, affecting membrane-protein interactions and cellular processes like vesiculation. This work provides critical insights into the molecular mechanisms by which hydroxylation influences membrane elasticity, with implications for both fundamental biophysics and therapeutic applications in cancer treatment.

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来源期刊

Chemistry and Physics of Lipids 生物-生化与分子生物学

CiteScore

7.60

自引率

2.90%

发文量

审稿时长

40 days

期刊介绍： Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications. Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.