Hassan Abdel-Rahman, Biel Thomas, Kim Taeyoon
Weldon School of Biomedical Engineering, Purdue University, 206 S. Martin Jischke Drive, West Lafayette, Indiana 47907, United States.
ACS Biomater Sci Eng. 2019 Aug 12;5(8):3954-3963. doi: 10.1021/acsbiomaterials.8b01365. Epub 2019 Mar 12.
Cell migration is a fundamental process in biological systems, playing an important role for diverse physiological processes. Cells often exhibit directed migration in a specific direction in response to various types of cues. In particular, cells are able to sense the rigidity of surrounding environments and then migrate toward stiffer regions. To understand this mechanosensitive behavior called durotaxis, several computational models have been developed. However, most of the models employed cell decision making to recapitulate durotactic behaviors, significantly limiting insights provided from these studies. In this study, we developed a computational biomechanical model without any cell decision making to illuminate intrinsic mechanisms of durotactic behaviors of cells migrating on a two-dimensional substrate. The model consists of a simplified cell generating contractile forces and a deformable substrate coarse-grained into an irregular triangulated mesh. Using the model, we demonstrated that durotactic behaviors emerge from purely mechanical interactions between the cell and the underlying substrate. We investigated how durotactic migration is regulated by biophysical properties of the substrate, including elasticity, viscosity, and stiffness profile.
细胞迁移是生物系统中的一个基本过程,对多种生理过程起着重要作用。细胞常常会响应各种类型的信号,在特定方向上表现出定向迁移。特别是,细胞能够感知周围环境的硬度,然后朝着更硬的区域迁移。为了理解这种称为趋硬性的机械敏感行为,人们已经开发了几种计算模型。然而,大多数模型采用细胞决策来概括趋硬行为,这显著限制了这些研究提供的见解。在本研究中,我们开发了一个没有任何细胞决策的计算生物力学模型,以阐明细胞在二维基质上迁移时趋硬行为的内在机制。该模型由一个产生收缩力的简化细胞和一个粗粒度化为不规则三角网格的可变形基质组成。利用该模型,我们证明了趋硬行为源于细胞与下层基质之间纯粹的机械相互作用。我们研究了趋硬迁移是如何受到基质的生物物理特性(包括弹性、粘度和硬度分布)调节的。