Ayee Manuela A A, Levitan Irena
Department of Engineering, Dordt University, Sioux Center, IA, United States.
Division of Pulmonary and Critical Care, Department of Medicine, University of Illinois at Chicago, Chicago, IL, United States.
Front Cardiovasc Med. 2021 Jul 16;8:715932. doi: 10.3389/fcvm.2021.715932. eCollection 2021.
Under hypercholesterolemic conditions, exposure of cells to lipoproteins results in a subtle membrane increase in the levels of cholesterol and 7-ketocholesterol, as compared to normal conditions. The effect of these physiologically relevant concentration increases on multicomponent bilayer membranes was investigated using coarse-grained molecular dynamics simulations. Significant changes in the structural and dynamic properties of the bilayer membranes resulted from these subtle increases in sterol levels, with both sterol species inducing decreases in the lateral area and inhibiting lateral diffusion to varying extents. Cholesterol and 7-ketocholesterol, however, exhibited opposite effects on lipid packing and orientation. The results from this study indicate that the subtle increases in membrane sterol levels induced by exposure to lipoproteins result in molecular-scale biophysical perturbation of membrane structure.
在高胆固醇血症条件下，与正常条件相比，细胞暴露于脂蛋白会导致细胞膜中胆固醇和7-酮胆固醇水平出现细微升高。使用粗粒度分子动力学模拟研究了这些生理相关浓度升高对多组分双层膜的影响。这些甾醇水平的细微升高导致双层膜的结构和动力学性质发生显著变化，两种甾醇都导致侧向面积减小并在不同程度上抑制侧向扩散。然而，胆固醇和7-酮胆固醇对脂质堆积和取向表现出相反的影响。这项研究的结果表明，暴露于脂蛋白诱导的膜甾醇水平的细微升高会导致膜结构的分子尺度生物物理扰动。
