Molecular Simulations of Mixed Lipid Bilayers with Sphingomyelin, Glycerophospholipids, and Cholesterol
Molecular Simulations of Mixed Lipid Bilayers with Sphingomyelin, Glycerophospholipids, and Cholesterol
复制标题
DOI：
10.1021/acs.jpcb.7b00359
复制
发表时间：
2017-05-25
影响因子：
3.3
通讯作者：
Klauda, Jeffery B.
中科院分区：
文献类型：
--
作者：
Bera, Indrani;Klauda, Jeffery B.
跨活细胞的脂质双层的高度多样化的组成对于许多生物过程是至关重要的。脂质双层主要由磷脂酰胆碱（PC）、磷脂酰乙醇胺（PE）、鞘磷脂（SM）和胆固醇组成，其中真核细胞膜含有高百分比的鞘磷脂和胆固醇。在这项研究中，我们模拟了不同浓度的PC，PE和SM的双层，以了解不同SM浓度的双层性质的变化。此外，还模拟了含33%胆固醇的膜模型，以了解胆固醇的影响。为了定量地获得膜的结构和动力学，计算氘序参数（Sap）、质量密度分布、脂质弛豫时间、聚类分析和径向分布函数。与过去的NMR实验相比，S（CD）s有利，并随着SM含量的增加而增加。表面积计算表明，添加50%棕榈酰-SM（PSM）后，表面积从纯POPC（64.7埃（2））降低（60.0 +/- 0.6埃（2）），在胆固醇存在下进一步降低（44.4 +/- 0.2埃（2））。脂质轴向弛豫时间随甘油磷脂浓度的增加而减小。这些脂质膜的准确性允许未来的研究与更复杂的脂质混合物含有SM代表天然膜中的脂质的多样性。
The highly diversified composition of lipid bilayers across living cells is crucial for many biological processes. Lipid bilayers mainly consist of phosphatidylcholines (PC), phosphatidylethanolamines (PE), sphingomyelin (SM), and cholesterol, with eukaryotic membranes containing high percentage of sphingomyelin and cholesterol. In this study, we have modeled bilayers with different concentration of PC, PE, and SM to understand the changes in bilayer properties with varied SM concentrations. In addition, membrane models with 33% cholesterol have been simulated to understand the influence of cholesterol. To quantitatively access the structure and dynamics of membranes, deuterium order parameters (Sap), mass density profiles,, lipid relaxation times, clustering analysis, and radial distribution functions are calculated. The S(CD)s compare favorably with past NMR experiments and increase with an increase in SM content. The surface area calculations showed that on addition of 50% palmitoyl-SM (PSM) surface area decreases (60.0 +/- 0.6 angstrom(2)) from that of pure POPC (64.7 angstrom(2)), which is further lowered in the presence of cholesterol (44.4 +/- 0.2 angstrom(2)). The lipid axial relaxation time decreases with increase in concentration of glycerophospholipids. The accuracy of these lipid membranes allows for future studies with more complex lipid mixtures containing SM to represent the diversity of lipids in natural membranes.