Confinement and substrate topography control cell migration in a 3D computational model
Confinement and substrate topography control cell migration in a 3D computational model
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DOI：
10.1038/s42005-019-0185-x
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发表时间：
2019-07
影响因子：
5.5
通讯作者：
B. Winkler;I. Aranson;F. Ziebert
中科院分区：
文献类型：
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作者：
B. Winkler;I. Aranson;F. Ziebert
体内细胞运动的典型特征是强限制和异质的三维环境。已知这种对细胞运动性的外部约束在许多重要过程中起重要作用，例如在发育、分化和免疫应答期间，以及在病理学如癌症转移中。在这里，我们开发了一个物理驱动的三维计算建模框架，该框架描述了在任意形状和地形结构的环境中细胞的基于板状体的运动。我们用它来调查目前实验研究的主要体外模型方案：在垂直限制，限制在微通道中的运动，以及纤维上的运动和施加调制的表面形貌。我们发现，限制，基板曲率和地形调制细胞的速度，形状和肌动蛋白组织，并可以引起运动方向的变化沿着轴所定义的约束。我们的模型作为一个基准，系统地探讨基于板状伪足的运动及其与环境的相互作用。
Cell movement in vivo is typically characterized by strong confinement and heterogeneous, three-dimensional environments. Such external constraints on cell motility are known to play important roles in many vital processes e.g. during development, differentiation, and the immune response, as well as in pathologies like cancer metastasis. Here we develop a physics-driven three-dimensional computational modeling framework that describes lamellipodium-based motion of cells in arbitrarily shaped and topographically structured surroundings. We use it to investigate the primary in vitro model scenarios currently studied experimentally: motion in vertical confinement, confinement in microchannels, as well as motion on fibers and on imposed modulations of surface topography. We find that confinement, substrate curvature and topography modulate the cell’s speed, shape and actin organization and can induce changes in the direction of motion along axes defined by the constraints. Our model serves as a benchmark to systematically explore lamellipodium-based motility and its interaction with the environment.