Department of Chemical and Biomolecular Engineering, Russ College of Engineering and Technology, Ohio University, Athens, OH 45701, USA.
Soft Matter. 2021 Mar 18;17(10):2742-2752. doi: 10.1039/d0sm01709d.
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.
真核细胞的质膜在组成上是不对称的。某些磷脂，如神经鞘磷脂和磷脂酰胆碱，主要定位于质膜的外叶，而磷脂酰乙醇胺和磷脂酰丝氨酸主要位于质膜的内叶。虽然质膜双层中外叶的磷脂不对称性已经得到证实，但关于双层中胆固醇的分布还没有共识。我们通过分子模拟，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主链、头部类型、不饱和度和链长的影响进行了系统研究，考虑了一种模拟红细胞质膜脂质的不对称双层，以及其他十七种由不同脂质类型组成的不对称双层。我们的结果表明，胆固醇在双层中的分布仅取决于双层中脂质的有序程度。胆固醇的含量比与双层中脂质有序性的比例相匹配，从而在两者之间提供了定量关系。这种关系可以通过观察到的现象来理解，即由于脂质有序性的差异，双层中含有等摩尔脂质的不对称双层会产生拉伸和压缩应力。这些应力通过将胆固醇从压缩应力的叶层转移到拉伸应力的叶层来缓解。这些发现对于理解细胞膜的生物学特性，特别是膜叶层的组成，非常重要。
