Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland.
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland; Center for Cell Dynamics, Johns Hopkins School of Medicine, Baltimore, Maryland.
Biophys J. 2023 Aug 22;122(16):3354-3368. doi: 10.1016/j.bpj.2023.07.011. Epub 2023 Jul 20.
Tissue cells in epithelial or endothelial monolayers are connected through cell-cell junctions, which are stabilized by transmembrane E-cadherin bonds and intracellular actin filaments. These bonds and junctions play a crucial role in maintaining the barrier function of epithelia and endothelia and are believed to transmit forces between cells. Additionally, E-cadherin bonds can impact the shape of cell-cell junctions. In this study, we develop a continuum mechanical model of the cell-cell junction by explicitly incorporating the cell membrane, distributions of E-cadherin bonds, cytoplasmic fluid pressure, and F-actin dynamics. The static force-balanced version of the model is able to analyze the influences of cell cortical tension, actin dynamics, and cytoplasmic pressure on the junction shape and E-cadherin bonds. Furthermore, an extended model that incorporates fluid flow, across the cell boundary as well as around the cell, is also examined. This model can couple cell-shape changes with cell cortical tension and fluid flow, and predicts the additional effect of fluid motion on cell-cell junction mechanics. Taken together, our models serve as an intermediate link between molecular-scale models of cell-junction molecules and cell-scale models of tissue and epithelia.
上皮或内皮单层组织细胞通过细胞-细胞连接相互连接,这些连接由跨膜 E-钙黏蛋白键和细胞内肌动蛋白丝稳定。这些连接和连接在维持上皮和内皮的屏障功能方面起着至关重要的作用,据信它们在细胞之间传递力。此外,E-钙黏蛋白键可以影响细胞-细胞连接的形状。在这项研究中,我们通过明确纳入细胞膜、E-钙黏蛋白键分布、细胞质流体压力和 F-肌动蛋白动力学,开发了细胞-细胞连接的连续力学模型。该模型的静态力平衡版本能够分析细胞皮质张力、肌动蛋白动力学和细胞质压力对连接形状和 E-钙黏蛋白键的影响。此外,还研究了包含跨细胞边界以及围绕细胞的流体流动的扩展模型。该模型可以将细胞形状变化与细胞皮质张力和流体流动相耦合,并预测流体运动对细胞-细胞连接力学的附加影响。总之,我们的模型在上皮和组织的细胞尺度模型与细胞连接分子的分子尺度模型之间起到了中间环节的作用。