Molecular dynamics simulations of lipid composition and its impact on structural and dynamic properties of skin membrane

IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Diyar Altun , Per Larsson , Christel A.S. Bergström , Shakhawath Hossain
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引用次数: 0

Abstract

The stratum corneum (SC) plays the most important role in the absorption of topical and transdermal drugs. In this study, we developed a multi-layered SC model using coarse-grained molecular dynamics (CGMD) simulations of ceramides, cholesterol, and fatty acids in equimolar proportions, starting from two different initial configurations. In the first approach, all ceramide molecules were initially in the hairpin conformation, and the membrane bilayers were pre-formed. In the second approach, ceramide molecules were introduced in either the hairpin or splayed conformation, with the lipid molecules randomly oriented at the start of the simulation. The aim was to evaluate the effects of lipid chain length on the structural and dynamic properties of SC. By incorporating ceramides and fatty acids of different chain lengths, we simulated the SC membrane in healthy and diseased states. We calculated key structural properties including the thickness, normalized lipid area, lipid tail order parameters, and spatial ordering of the lipids from each system. The results showed that systems with higher ordering and structural integrity contained an equimolar ratio of ceramides (chain length of 24 carbon atoms), fatty acids with chain lengths ≥ of 20 carbon atoms, and cholesterol. In these systems, strong apolar interactions between the ceramide and fatty acid long acyl chains restricted the mobility of the lipid molecules, thereby maintaining a compact lipid headgroup region and high order in the lipid tail region. The simulations also revealed distinct flip-flop mechanisms for cholesterol and fatty acid within the multi-layered membrane. Cholesterol is mostly diffused through the tail-tail interface region of the membrane and could flip-flop in the same bilayer. In contrast, fatty acids flip-flopped between adjacent leaflets of two bilayers in which the tails crossed the thinner headgroup region of the membrane. To conclude, our SC model provides mechanistic insights into lipid mobility and is flexible in its design and composition of different lipids, enabling studies of varying skin conditions.
脂质组成及其对皮肤膜结构和动态特性影响的分子动力学模拟。
角质层(SC)在外用药物和透皮药物的吸收过程中发挥着最重要的作用。在这项研究中,我们从两种不同的初始构型出发,利用粗粒度分子动力学(CGMD)模拟等摩尔比例的神经酰胺、胆固醇和脂肪酸,建立了一个多层角质层模型。在第一种方法中,所有神经酰胺分子最初都处于发夹构象,膜双层也是预先形成的。在第二种方法中,神经酰胺分子被引入发夹构象或平展构象,脂质分子在模拟开始时随机定向。目的是评估脂质链长度对 SC 结构和动态特性的影响。通过加入不同链长的神经酰胺和脂肪酸,我们模拟了健康和疾病状态下的 SC 膜。我们计算了每个系统的主要结构特性,包括厚度、归一化脂质面积、脂质尾部有序参数和脂质的空间有序性。结果表明,具有较高有序性和结构完整性的系统含有等摩尔比例的神经酰胺(链长为 24 个碳原子)、链长≥ 20 个碳原子的脂肪酸和胆固醇。在这些系统中,神经酰胺和脂肪酸长酰基链之间强烈的极性相互作用限制了脂质分子的流动性,从而保持了脂质头部的紧凑性和脂质尾部的高有序性。模拟还揭示了胆固醇和脂肪酸在多层膜内不同的翻转机制。胆固醇主要通过膜的尾部界面区域扩散,可以在同一双分子层中翻转。与此相反,脂肪酸在两个双层膜的相邻小叶之间翻转,其中尾部穿过膜的较薄的头组区。总之,我们的 SC 模型从机理上揭示了脂质的流动性,而且在设计和不同脂质的组成方面非常灵活,可以对不同的皮肤条件进行研究。
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
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
50
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.
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