Department of Chemical and Biomolecular engineering, University of Pennsylvania, Philadelphia, PA 19104, United States of America.
Phys Biol. 2019 Oct 21;16(6):066011. doi: 10.1088/1478-3975/ab48d5.
The morphologies of cell membranes, and specifically the local curvature distributions are determined either by its intrinsic components such as lipids and membrane-associated proteins or by the adhesion forces due to membrane interactions with the cytoskeleton, extracellular matrix (ECM) and other cells in the tissue, as well as physical variables such as membrane and frame tensions. We present a computational analysis for a model of pinned membranes based on the dynamically triangulated Monte Carlo (MC) model for membranes. We show that membrane adhesion to ECM or a substrate promotes curvature generation on cell membranes, and this process depends on the excess area, or equivalently membrane tension, and the density of adhesion sites. This biophysics based model predicts adhesion induced biogenesis of microvesicles in cell membranes. For a moderate density of adhesion sites and high excess membrane area, an increase in membrane tension can result in the formation of microvesicles and tubules on the membrane. We also demonstrate the significance of intrinsically curved proteins in promoting vesiculation on pinned membranes. The results presented here are relevant to the understanding of microvesicle biogenesis and curved membrane topographies due to physical factors such as substrate stiffness and ECM interactions.
细胞膜的形态,特别是局部曲率分布,由其内在成分(如脂质和膜相关蛋白)决定,或者由细胞膜与细胞骨架、细胞外基质(ECM)和组织中其他细胞之间的粘附力决定,以及膜和框架张力等物理变量。我们提出了一种基于动态三角化蒙特卡罗(MC)模型的固定膜模型的计算分析。我们表明,细胞膜与 ECM 或基质的粘附促进细胞膜上的曲率产生,这个过程取决于过剩面积(等效于膜张力)和粘附位点的密度。这个基于生物物理的模型预测了细胞膜中粘附诱导的微泡生物发生。对于中等密度的粘附位点和高过剩膜面积,膜张力的增加会导致膜上微泡和小管的形成。我们还证明了内在弯曲蛋白在促进固定膜上囊泡形成中的重要性。这里呈现的结果与理解由于物理因素(如基质刚度和 ECM 相互作用)引起的微泡生物发生和弯曲膜形貌有关。