Quantitative relationship between cholesterol distribution and ordering of lipids in asymmetric lipid bilayers
Quantitative relationship between cholesterol distribution and ordering of lipids in asymmetric lipid bilayers
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DOI：
10.1039/d0sm01709d
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发表时间：
2021-03-14
期刊：
影响因子：
3.4
通讯作者：
Sharma, Sumit
中科院分区：
文献类型：
--
作者：
Aghaaminiha, Mohammadreza;Farnoud, Amir M.;Sharma, Sumit
已知真核细胞的质膜在成分上是不对称的。某些磷脂，例如鞘磷脂和磷脂酰胆碱种类，主要位于外叶中，而磷脂酰乙醇胺和磷脂酰丝氨酸种类主要存在于内叶中。虽然膜小叶之间的磷脂不对称性已得到充分证实，但对于两个小叶之间的胆固醇分布尚未达成共识。我们通过分子模拟，通过考虑模拟红细胞质膜脂质的不对称双层以及由不同脂质类型组成的其他十七个不对称双层，对不同“不对称”脂质双层中胆固醇分子的空间分布如何受到脂质骨架、头型、不饱和度和链长度的影响进行了系统研究。我们的结果表明，小叶中胆固醇的分布仅是小叶内脂质排序程度的函数。胆固醇含量的比例与两个小叶中脂质顺序的比例相匹配，从而提供了两者之间的定量关系。这些结果可以通过以下观察来理解：由于脂质有序程度的差异，两个小叶中具有等摩尔量脂质的不对称双层产生拉应力和压应力。这些压力通过胆固醇从压缩应力下的小叶转移到拉伸应力下的小叶而得到缓解。这些发现对于理解细胞膜的生物学非常重要，特别是在膜小叶的组成方面。
The plasma membrane of eukaryotic cells is known to be compositionally asymmetric. Certain phospholipids, such as sphingomyelin and phosphatidylcholine species, are predominantly localized in the outer leaflet, while phosphatidylethanolamine and phosphatidylserine species primarily reside in the inner leaflet. While phospholipid asymmetry between the membrane leaflets is well established, there is no consensus about cholesterol distribution between the two leaflets. We have performed a systematic study, via molecular simulations, of how the spatial distribution of cholesterol molecules in different "asymmetric" lipid bilayers are affected by the lipids' backbone, head-type, unsaturation, and chain-length by considering an asymmetric bilayer mimicking the plasma membrane lipids of red blood cells, as well as seventeen other asymmetric bilayers comprising of different lipid types. Our results reveal that the distribution of cholesterol in the leaflets is solely a function of the extent of ordering of the lipids within the leaflets. The ratio of the amount of cholesterol matches the ratio of lipid order in the two leaflets, thus providing a quantitative relationship between the two. These results are understood by the observation that asymmetric bilayers with equimolar amount of lipids in the two leaflets develop tensile and compressive stresses due to differences in the extent of lipid order. These stresses are alleviated by the transfer of cholesterol from the leaflet in compressive stress to the one in tensile stress. These findings are important in understanding the biology of the cell membrane, especially with regard to the composition of the membrane leaflets.