The Functional Significance of Lipid Diversity: Orientation of Cholesterol in Bilayers Is Determined by Lipid Species
The Functional Significance of Lipid Diversity: Orientation of Cholesterol in Bilayers Is Determined by Lipid Species
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DOI：
10.1021/ja907659u
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发表时间：
2009-11-18
影响因子：
15
通讯作者：
Katsaras, John
中科院分区：
文献类型：
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作者：
Kucerka, Norbert;Marquardt, Drew;Katsaras, John
脂类的化学多样性及其在超分子组装中的复杂排列与我们以前认为它们是被动结构成分的概念形成了鲜明对比。例如，在质膜中，鞘磷脂主要位于外单层，而不饱和磷脂在1：内叶中更为丰富。我们最近的研究结果对生物膜中脂质多样性的重要性做出了直接的贡献。我们研究了不同含量的单不饱和(POPC)和不饱和(DMPC)脂在多不饱和脂肪酸(PUFA)双层膜中胆固醇的位置。利用氚标记和中子衍射，我们发现在PUFA双层膜中，只需改变POPC的量，胆固醇就可以从它在双层中心的已知位置反转到它通常认为的垂直方向。虽然翻转PUFA双层中的胆固醇需要类似于50mol%的POPC，但只需5mol%的DMPC就能达到同样的效果，优雅地强调了胆固醇对饱和链的亲和力。这也表明，细胞双层内叶中多不饱和脂肪酸的存在可能会促进胆固醇向外层的转移，从而潜在地改变RAFT的组成和膜的局部功能。
The chemical diversity of Lipids and their complex arrangements in supramolecular assemblies are in stark contrast to our previous notions of them as passive structural components. For example, in plasma membranes, sphingolipids are primarily located in the outer monolayer, whereas unsaturated phospholipids are more abundant in the 1: inner leaflet. Our recent results offer a direct contribution to the importance of lipid diversity in biological membranes. We have studied the location of cholesterol within polyunsaturated fatty acid (PUFA) bilayers doped with different amounts of monounsaturated (POPC) or disaturated (DMPC) lipids. Using deuterium labeling and neutron diffraction, we have found that in PUFA bilayers, cholesterol can be flipped from its known position in the bilayer center to its commonly assumed upright orientation simply by varying the amount of POPC. Although it takes similar to 50 mol % POPC to flip cholesterol in PUFA bilayers, the same effect is achieved with only 5 mol % DMPC, elegantly emphasizing cholesterol's affinity for saturated chains. It also suggests that the presence of PUFA in the inner leaflet of a cellular bilayer may enhance the transfer of cholesterol to the outer layer, potentially modifying raft composition and the local function of a membrane.