Polyunsaturated Lipids Regulate Membrane Domain Stability by Tuning Membrane Order
Polyunsaturated Lipids Regulate Membrane Domain Stability by Tuning Membrane Order
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DOI：
10.1016/j.bpj.2016.03.012
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发表时间：
2016-04-26
影响因子：
3.4
通讯作者：
Levental, Ilya
中科院分区：
文献类型：
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作者：
Levental, Kandice R.;Lorent, Joseph H.;Levental, Ilya
质膜（PM）作为细胞与其环境之间的功能界面，在各种其他过程中主持细胞外信号转导和营养物质运输。为了支持这一广泛的功能，PM被组织成横向域，包括有序的，脂质驱动的组件称为脂筏。虽然有序结构域形成的一般要求是明确的，但这些结构域如何受到细胞内源性机制或外源性扰动的调节尚未得到广泛解决。在这种情况下，一个有趣的可能性是，膳食脂肪可以纳入膜脂质调节筏域的性质和生理。在这里，我们调查的影响，多不饱和脂肪对组织的膜结构域跨频谱的膜模型，包括计算机模拟，合成脂质膜，和完整的PM分离的哺乳动物细胞。我们观察到，ω-3多不饱和脂肪酸二十二碳六烯酸被稳健地掺入膜脂质中，并且这种掺入导致PM脂质体的显著重塑。在整个模型系统中，含有二十二碳六烯酸的脂质通过增加它们与共存的非筏结构域之间的顺序差异来增强有序筏结构域的稳定性。域间的顺序差异和相分离的稳定性之间的关系，持有不同的扰动，包括操纵胆固醇水平和高浓度的外源性两亲物的光谱，这表明它作为一个一般特征的组织的生物膜。这些结果表明，多不饱和脂肪影响生物膜的组成和组织，这表明膳食脂肪对健康和疾病的广泛影响的潜在机制。
The plasma membrane (PM) serves as the functional interface between a cell and its environment, hosting extracellular signal transduction and nutrient transport among a variety of other processes. To support this extensive functionality, PMs are organized into lateral domains, including ordered, lipid-driven assemblies termed lipid rafts. Although the general requirements for ordered domain formation are well established, how these domains are regulated by cell-endogenous mechanisms or exogenous perturbations has not been widely addressed. In this context, an intriguing possibility is that dietary fats can incorporate into membrane lipids to regulate the properties and physiology of raft domains. Here, we investigate the effects of polyunsaturated fats on the organization of membrane domains across a spectrum of membrane models, including computer simulations, synthetic lipid membranes, and intact PMs isolated from mammalian cells. We observe that the omega-3 polyunsaturated fatty acid docosahexaenoic acid is robustly incorporated into membrane lipids, and this incorporation leads to significant remodeling of the PM lipidome. Across model systems, docosahexaenoic acid-containing lipids enhance the stability of ordered raft domains by increasing the order difference between them and coexisting nonraft domains. The relationship between interdomain order disparity and the stability of phase separation holds for a spectrum of different perturbations, including manipulation of cholesterol levels and high concentrations of exogenous amphiphiles, suggesting it as a general feature of the organization of biological membranes. These results demonstrate that polyunsaturated fats affect the composition and organization of biological membranes, suggesting a potential mechanism for the extensive effects of dietary fat on health and disease.