Research School of Chemistry, College of Science, The Australian National University, Canberra, ACT 2601, Australia.
J Chem Phys. 2021 Mar 7;154(9):095101. doi: 10.1063/5.0040887.
A coarse-grain model of the epithelial plasma membrane was developed from high-resolution lipidomic data and simulated using the MARTINI force field to characterize its biophysical properties. Plasmalogen lipids, Forssman glycosphingolipids, and hydroxylated Forssman glycosphingolipids and sphingomyelin were systematically added to determine their structural effects. Plasmalogen lipids have a minimal effect on the overall biophysical properties of the epithelial plasma membrane. In line with the hypothesized role of Forssman lipids in the epithelial apical membrane, the introduction of Forssman lipids initiates the formation of glycosphingolipid-rich nanoscale lipid domains, which also include phosphatidylethanolamine (PE), sphingomyelin (SM), and cholesterol (CHOL). This decreases the lateral diffusion in the extracellular leaflet, as well as the area per lipid of domain forming lipids, most notably PE. Finally, hydroxylation of the Forssman glycosphingolipids and sphingomyelin further modulates the lateral organization of the membrane. Through comparison to the previously studied average and neuronal plasma membranes, the impact of membrane lipid composition on membrane properties was characterized. Overall, this study furthers our understanding of the biophysical properties of complex membranes and the impact of lipid diversity in modulating membrane properties.
从高分辨率脂质组学数据中开发了上皮质膜的粗粒度模型，并使用 MARTINI 力场进行模拟，以表征其生物物理特性。系统地添加了脑苷脂脂质、福斯曼糖脂、羟基化福斯曼糖脂和神经鞘磷脂，以确定它们的结构效应。脑苷脂脂质对上皮质膜的整体生物物理特性的影响最小。与福斯曼脂质在上皮质顶膜中的假设作用一致，福斯曼脂质的引入引发富含糖脂的纳米尺度脂质域的形成，其中还包括磷脂酰乙醇胺 (PE)、神经鞘磷脂 (SM) 和胆固醇 (CHOL)。这会降低细胞外叶层的侧向扩散，以及形成脂质域的脂质的每脂质面积，尤其是 PE。最后，福斯曼糖脂和神经鞘磷脂的羟基化进一步调节膜的侧向组织。通过与之前研究的平均和神经元质膜进行比较，表征了膜脂质组成对膜性质的影响。总的来说，这项研究进一步加深了我们对复杂膜的生物物理特性以及脂质多样性在调节膜性质方面的影响的理解。
