Leekumjorn Sukit, Cho Hyun Ju, Wu Yifei, Wright Neil T, Sum Amadeu K, Chan Christina
Department of Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Biochim Biophys Acta. 2009 Jul;1788(7):1508-16. doi: 10.1016/j.bbamem.2009.04.002. Epub 2009 Apr 14.
Studying the effects of saturated and unsaturated fatty acids on biological and model (liposomes) membranes could provide insight into the contribution of biophysical effects on the cytotoxicity observed with saturated fatty acids. In vitro experiments suggest that unsaturated fatty acids, such as oleate and linoleate, are less toxic, and have less impact on the membrane fluidity. To understand and assess the biophysical changes in the presence of the different fatty acids, we performed computational analyses of model liposomes with palmitate, oleate, and linoleate. The computational results indicate that the unsaturated fatty acid chain serves as a membrane stabilizer by preventing changes to the membrane fluidity. Based on a Voronoi tessellation analysis, unsaturated fatty acids have structural properties that can reduce the lipid ordering within the model membranes. In addition, hydrogen bond analysis indicates a more uniform level of membrane hydration in the presence of oleate and linoleate as compared to palmitate. Altogether, these observations from the computational studies provide a possible mechanism by which unsaturated fatty acids minimize biophysical changes and protect the cellular membrane and structure. To corroborate our findings, we also performed a liposomal leakage study to assess how the different fatty acids alter the membrane integrity of liposomes. This showed that palmitate, a saturated fatty acid, caused greater destabilization of liposomes (more "leaky") than oleate, an unsaturated fatty acid.
研究饱和脂肪酸和不饱和脂肪酸对生物膜及模型膜(脂质体)的影响,有助于深入了解生物物理效应在饱和脂肪酸细胞毒性中所起的作用。体外实验表明,不饱和脂肪酸,如油酸酯和亚油酸酯,毒性较小,对膜流动性的影响也较小。为了理解和评估不同脂肪酸存在时的生物物理变化,我们对含有棕榈酸酯、油酸酯和亚油酸酯的模型脂质体进行了计算分析。计算结果表明,不饱和脂肪酸链可通过防止膜流动性变化来充当膜稳定剂。基于Voronoi镶嵌分析,不饱和脂肪酸具有能降低模型膜内脂质有序性的结构特性。此外,氢键分析表明,与棕榈酸酯相比,油酸酯和亚油酸酯存在时膜水合作用水平更均匀。总之,这些计算研究的观察结果提供了一种可能的机制,即不饱和脂肪酸可将生物物理变化降至最低,并保护细胞膜和细胞结构。为了证实我们的发现,我们还进行了脂质体泄漏研究,以评估不同脂肪酸如何改变脂质体的膜完整性。结果表明,饱和脂肪酸棕榈酸酯比不饱和脂肪酸油酸酯更能使脂质体不稳定(更“易渗漏”)。
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