Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland.
Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland; Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland; Johns Hopkins Physical Sciences-Oncology Center, Johns Hopkins University, Baltimore, Maryland.
Biophys J. 2018 Jun 19;114(12):2965-2973. doi: 10.1016/j.bpj.2018.04.045.
Cells in vivo can reside in diverse physical and biochemical environments. For example, epithelial cells typically live in a two-dimensional (2D) environment, whereas metastatic cancer cells can move through dense three-dimensional matrices. These distinct environments impose different kinds of mechanical forces on cells and thus potentially can influence the mechanism of cell migration. For example, cell movement on 2D flat surfaces is mostly driven by forces from focal adhesion and actin polymerization, whereas in confined geometries, it can be driven by water permeation. In this work, we utilize a two-phase model of the cellular cytoplasm in which the mechanics of the cytosol and the F-actin network are treated on an equal footing. Using conservation laws and simple force balance considerations, we are able to describe the contributions of water flux, actin polymerization and flow, and focal adhesions to cell migration both on 2D surfaces and in confined spaces. The theory shows how cell migration can seamlessly transition from a focal adhesion- and actin-based mechanism on 2D surfaces to a water-based mechanism in confined geometries.
细胞在体内可以存在于不同的物理和生化环境中。例如,上皮细胞通常生活在二维(2D)环境中,而转移性癌细胞可以穿过密集的三维基质。这些不同的环境对细胞施加不同种类的机械力,因此可能会影响细胞迁移的机制。例如,细胞在 2D 平坦表面上的运动主要是由来自焦点黏附和肌动蛋白聚合的力驱动的,而在受限的几何形状中,它可以由水渗透驱动。在这项工作中,我们利用细胞细胞质的两相模型,其中细胞质和 F-肌动蛋白网络的力学被平等对待。利用守恒定律和简单的力平衡考虑,我们能够描述水通量、肌动蛋白聚合和流动以及焦点黏附在 2D 表面和受限空间中对细胞迁移的贡献。该理论展示了细胞迁移如何从 2D 表面上基于焦点黏附和肌动蛋白的机制无缝过渡到受限几何形状中的基于水的机制。