Domain Stability in Biomimetic Membranes Driven by Lipid Polyunsaturation.
Domain Stability in Biomimetic Membranes Driven by Lipid Polyunsaturation.
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DOI：
10.1021/acs.jpcb.6b06815
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发表时间：
2016-11-23
期刊：
影响因子：
--
通讯作者：
Levental I
中科院分区：
文献类型：
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作者：
Lin X;Lorent JH;Skinkle AD;Levental KR;Waxham MN;Gorfe AA;Levental I
生物膜包含多种脂质种类，其各自的物理化学性质以及集体相互作用最终决定了膜的组织形式。细胞膜组织的一个关键方面是它们在横向细分为具有不同结构和组成的区域。研究最为广泛的膜区域是脂筏，它是在含固醇的膜中形成的有序液相的生物学表现形式。对仿生膜混合物的详细研究已经对脂筏背后的物理原理有了广泛的认识；然而，这些简化的模型并不能完全捕捉哺乳动物脂质组的多样性和复杂性，最显著的是它们排除了多不饱和脂质。在这里，我们通过粗粒化分子动力学（CGMD）模拟并结合模型膜实验进行验证，来评估脂质酰基链不饱和度作为相分离驱动力的作用。我们观察到的明显趋势以及模拟和实验之间良好的定性一致性支持了以下结论：高度不饱和的脂质通过增强共存区域之间胆固醇含量的差异以及由此产生的脂质链有序性来促进液 - 液相区域的稳定性。这些观察结果揭示了非经典生物脂质在膜物理性质中的重要作用，表明脂质多不饱和性是液 - 液相分离的驱动力。
Biological membranes contain a broad variety of lipid species whose individual physicochemical properties and collective interactions ultimately determine membrane organization. A key aspect of the organization of cellular membranes is their lateral subdivision into domains of distinct structure and composition. The most widely studied membrane domains are lipid rafts, which are the biological manifestations of liquid-ordered phases that form in sterol-containing membranes. Detailed studies of biomimetic membrane mixtures have yielded wide-ranging insights into the physical principles behind lipid rafts; however, these simplified models do not fully capture the diversity and complexity of the mammalian lipidome, most notably in their exclusion of polyunsaturated lipids. Here, we assess the role of lipid acyl chain unsaturation as a driving force for phase separation using coarse-grained molecular dynamics (CGMD) simulations validated by model membrane experiments. The clear trends in our observations and good qualitative agreements between simulations and experiments support the conclusions that highly unsaturated lipids promote liquid-liquid domain stability by enhancing the differences in cholesterol content and resulting lipid chain order between the coexisting domains. These observations reveal the important role of non-canonical biological lipids in the physical properties of membranes, showing that lipid polyunsaturation is a driving force for liquid-liquid phase separation.