A theoretical model of collective cell polarization and alignment.
A theoretical model of collective cell polarization and alignment.
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DOI：
10.1016/j.jmps.2019.103860
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发表时间：
2020-04
影响因子：
5.3
通讯作者：
Shijie He;Yoav Green;N. Saeidi;Xiaojun Li;J. Fredberg;B. Ji;L. Pismen
中科院分区：
文献类型：
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作者：
Shijie He;Yoav Green;N. Saeidi;Xiaojun Li;J. Fredberg;B. Ji;L. Pismen
集体细胞极化和排列在组织形态发生、伤口愈合和癌症转移中起重要作用。然而，细胞在这些过程中如何感知方向和位置还没有完全理解。本文将细胞层描述为弹性介质，建立了一个理论模型，将细胞极化、细胞排列和细胞主动收缩明确表示为有序参数分量的函数。为了确定序参数，我们推导出两套控制方程，一个用于系统的力平衡，另一个用于系统的自由能最小化，包括细胞极化和排列的能量。通过求解这些耦合的控制方程，我们可以预测基板的刚度，几何形状的细胞层，外力和肌球蛋白活性的方向和位置依赖的细胞纵横比和细胞取向的影响。此外，轴对称问题的细胞上的环状图案解析解决，和解析解的细胞长宽比的参数组，其中包括细胞和基板的刚度，肌球蛋白活性的强度和外力。我们的预测细胞的纵横比和方向一般与实验观察。这些结果表明，细胞极化的模式是由主动收缩应力的各向异性程度，并建议应力驱动的极化机制，使细胞能够感觉到他们的空间位置，发展方向和位置依赖性行为。这反过来又揭示了在组织工程中控制图案形成的方法，以用于潜在的生物医学应用。
Collective cell polarization and alignment play important roles in tissue morphogenesis, wound healing and cancer metastasis. How cells sense the direction and position in these processes, however, has not been fully understood. Here we construct a theoretical model based on describing cell layer as a nemato-elastic medium, by which the cell polarization, cell alignment and cell active contraction are explicitly expressed as functions of components of the nematic order parameter. To determine the order parameter we derive two sets of governing equations, one for the force equilibrium of the system, and the other for the minimization of the system's free energy including the energy of cell polarization and alignment. By solving these coupled governing equations, we can predict the effects of substrate stiffness, geometries of cell layers, external forces and myosin activity on the direction- and position-dependent cell aspect ratio and cell orientation. Moreover, the axisymmetric problem with cells on a ring-like pattern is solved analytically, and the analytical solution for cell aspect ratio are governed by parameter groups which include the stiffness of the cell and the substrate, the strength of myosin activity and the external forces. Our predictions of the cell aspect ratio and orientation are generally comparable to experimental observations. These results show that the pattern of cell polarization is determined by the anisotropic degree of active contractile stress, and suggest a stress-driven polarization mechanism that enables cells to sense their spatial positions to develop direction- and position-dependent behavior. This, in turn, sheds light on the ways to control pattern formation in tissue engineering for potential biomedical applications.