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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弯曲规则：2-羟基油酸羟基化鞘脂膜的分子动力学。

在这项研究中，我们引入了一种新的方法来量化脂质膜的力学性能-弯曲刚度（κ），高斯刚度（κ g）和表面张力（γ）使用分子动力学（MD）模拟。我们的方法被应用于含有2-羟基油酸（2OHOA）的膜，这是一种合成油酸衍生物，目前正在临床研究其抗癌特性。2OHOA改变癌细胞的质膜组成，激活鞘磷脂合成酶1 (SMS1)，这是维持质膜鞘脂水平的关键酶。本研究的重点是将2OHOA整合到神经酰胺和鞘磷脂中，如何改变这些膜的力学和生物物理特性。我们使用MD模拟来分析结构参数，如脂质面积、体积和双层厚度。此外，通过构建基于hellich - seifert模型的线性方程组，我们估计了羟基化膜与非羟基化膜的力学性能。我们的研究结果表明，由于羟基化作用，膜刚度和曲率发生了显著变化，影响了膜-蛋白相互作用和细胞过程，如泡化。这项工作为羟基化影响膜弹性的分子机制提供了重要的见解，对基础生物物理学和癌症治疗中的治疗应用都有意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.