Weldon School of Biomedical Engineering, Purdue University, 206 S. Martin Jischke Drive, West Lafayette, IN, 47907, USA.
Department of Agricultural and Biological Engineering, Purdue University, 225 South University Street, West Lafayette, IN, 47907, USA.
Bull Math Biol. 2019 Aug;81(8):3301-3321. doi: 10.1007/s11538-019-00585-1. Epub 2019 Feb 20.
Cell migration plays an important role in physiology and pathophysiology. It was observed in the experiments that cells, such as fibroblast, leukocytes, and cancer cells, exhibit a wide variety of migratory behaviors, such as persistent random walk, contact inhibition of locomotion, and ordered behaviors. To identify biophysical mechanisms for these cellular behaviors, we developed a rigorous computational model of cell migration on a two-dimensional non-deformable substrate. Cells in the model undergo motion driven by mechanical interactions between cellular protrusions and the substrate via the balance of tensile forces. Properties of dynamic formation of lamellipodia induced the persistent random walk behavior of a migrating cell. When multiple cells are included in the simulation, the model recapitulated the contact inhibition of locomotion between cells at low density without any phenomenological assumptions or momentum transfer. Instead, the model showed that contact inhibition of locomotion can emerge via indirect interactions between the cells through their interactions with the underlying substrate. At high density, contact inhibition of locomotion between numerous cells gave rise to confined motions or ordered behaviors, depending on cell density and how likely lamellipodia turn over due to contact with other cells. Results in our study suggest that various collective migratory behaviors may emerge without more restrictive assumptions or direct cell-to-cell biomechanical interactions.
细胞迁移在生理和病理生理学中起着重要作用。在实验中观察到，细胞（如成纤维细胞、白细胞和癌细胞）表现出多种迁移行为，如持续的随机游走、运动的接触抑制和有序行为。为了确定这些细胞行为的生物物理机制，我们在二维不可变形的基质上开发了一个严格的细胞迁移计算模型。模型中的细胞通过细胞突起与基质之间的张力平衡来驱动运动。斑片状伪足的动态形成特性诱导了迁移细胞的持续随机游走行为。当多个细胞被包含在模拟中时，该模型在没有任何唯象假设或动量传递的情况下再现了低细胞密度下细胞间的运动接触抑制。相反，该模型表明，通过细胞与基底之间的间接相互作用，可以出现运动接触抑制。在高密度下，由于与其他细胞接触而导致的大量细胞之间的运动接触抑制导致受限运动或有序行为，这取决于细胞密度和斑片状伪足由于接触而翻转的可能性。我们的研究结果表明，各种集体迁移行为可能在没有更严格的假设或直接的细胞间生物力学相互作用的情况下出现。
