Dabagh Mahsa, Jalali Payman, Butler Peter J, Tarbell John M
School of Technology, Lappeenranta University of Technology, Lappeenranta, Finland
School of Technology, Lappeenranta University of Technology, Lappeenranta, Finland.
J R Soc Interface. 2014 Sep 6;11(98):20140431. doi: 10.1098/rsif.2014.0431.
Haemodynamic forces applied at the apical surface of vascular endothelial cells (ECs) provide the mechanical signals at intracellular organelles and through the inter-connected cellular network. The objective of this study is to quantify the intracellular and intercellular stresses in a confluent vascular EC monolayer. A novel three-dimensional, multiscale and multicomponent model of focally adhered ECs is developed to account for the role of potential mechanosensors (glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs) and adherens junctions (ADJs)) in mechanotransmission and EC deformation. The overriding issue addressed is the stress amplification in these regions, which may play a role in subcellular localization of mechanotransmission. The model predicts that the stresses are amplified 250-600-fold over apical values at ADJs and 175-200-fold at FAs for ECs exposed to a mean shear stress of 10 dyne cm(-2). Estimates of forces per molecule in the cell attachment points to the external cellular matrix and cell-cell adhesion points are of the order of 8 pN at FAs and as high as 3 pN at ADJs, suggesting that direct force-induced mechanotransmission by single molecules is possible in both. The maximum deformation of an EC in the monolayer is calculated as 400 nm in response to a mean shear stress of 1 Pa applied over the EC surface which is in accord with measurements. The model also predicts that the magnitude of the cell-cell junction inclination angle is independent of the cytoskeleton and glycocalyx. The inclination angle of the cell-cell junction is calculated to be 6.6° in an EC monolayer, which is somewhat below the measured value (9.9°) reported previously for ECs subjected to 1.6 Pa shear stress for 30 min. The present model is able, for the first time, to cross the boundaries between different length scales in order to provide a global view of potential locations of mechanotransmission.
施加于血管内皮细胞（ECs）顶端表面的血流动力学力在细胞内细胞器以及通过相互连接的细胞网络提供机械信号。本研究的目的是量化汇合的血管内皮细胞单层中的细胞内和细胞间应力。开发了一种新的三维、多尺度和多组分的局灶性粘附内皮细胞模型，以解释潜在的机械传感器（糖萼层、肌动蛋白皮质层、细胞核、细胞骨架、粘着斑（FAs）和紧密连接（ADJs））在机械转导和内皮细胞变形中的作用。所解决的首要问题是这些区域的应力放大，这可能在机械转导的亚细胞定位中起作用。该模型预测，对于暴露于10达因/厘米²平均剪切应力的内皮细胞，在紧密连接处应力比顶端值放大250 - 600倍，在粘着斑处放大175 - 200倍。细胞与外部细胞基质的附着点以及细胞 - 细胞粘附点处每个分子的力估计在粘着斑处约为8皮牛，在紧密连接处高达3皮牛，这表明在两者中单个分子通过直接力诱导的机械转导都是可能的。响应于施加在EC表面的1帕平均剪切应力，单层中内皮细胞的最大变形计算为400纳米，这与测量结果一致。该模型还预测细胞 - 细胞连接倾斜角的大小与细胞骨架和糖萼无关。计算得出内皮细胞单层中细胞 - 细胞连接的倾斜角为6.6°，略低于先前报道的在1.6帕剪切应力下作用30分钟的内皮细胞的测量值（9.9°）。本模型首次能够跨越不同长度尺度的边界，以便提供机械转导潜在位置的全局视图。
