Division of Pulmonary Care, Department of Medicine, University of Illinois at Chicago.
Division of Pulmonary Care, Department of Medicine, University of Illinois at Chicago,
Front Biosci (Landmark Ed). 2016 Jun 1;21(6):1245-59. doi: 10.2741/4454.
Cell stiffness or deformability is a fundamental property that is expected to play a major role in multiple cellular functions. It is well known that cell stiffness is dominated by the intracellular cytoskeleton that, together with the plasma membrane, forms a membrane-cytoskeleton envelope. However, our understanding of how lipid composition of plasma membrane regulates physical properties of the underlying cytoskeleton is only starting to emerge. In this review, we first briefly describe the impact of cholesterol on the physical properties of lipid bilayers in model membranes and in living cells, with the dominant effect of increasing the order of membrane lipids and decreasing membrane fluidity. Then, we discuss accumulating evidence that removal of cholesterol, paradoxically, decreases the mobility of membrane proteins and increases cellular stiffness, with both effects being dependent on the integrity of the cytoskeleton. Finally, we discuss emerging evidence that oxidized modifications of low-density lipoproteins (oxLDL) have the same effects on endothelial biomechanical properties as cholesterol depletion, an effect that is mediated by the incorporation of oxysterols into the membrane.
细胞刚性或变形性是一种基本特性,预计将在多种细胞功能中发挥主要作用。众所周知,细胞刚性主要由细胞内细胞骨架决定,细胞骨架与质膜一起形成膜-细胞骨架包膜。然而,我们对于质膜的脂质组成如何调节下衬细胞骨架的物理性质的理解才刚刚开始显现。在这篇综述中,我们首先简要描述胆固醇对模型膜和活细胞中脂质双层物理性质的影响,其主要作用是增加膜脂质的有序性并降低膜流动性。然后,我们讨论了越来越多的证据表明,去除胆固醇会反使膜蛋白的流动性降低,细胞刚性增加,这两种效应都依赖于细胞骨架的完整性。最后,我们讨论了新出现的证据,即氧化修饰的低密度脂蛋白(oxLDL)对内皮细胞生物力学特性的影响与胆固醇耗竭相同,这种作用是通过将氧化固醇掺入膜中来介导的。