Collective cell migration is an essential phenomenon in many naturally occurring pathophysiological processes, as well as in tissue engineering applications. Cells in tissues and organs are known to sense chemical and mechanical signals from the microenvironment and collectively respond to these signals. For the last few decades, the effects of chemical signals such as growth factors and therapeutic agents on collective cell behaviors in the context of tissue engineering have been extensively studied, whereas those of the mechanical cues have only recently been investigated. The mechanical signals can be presented to the constituent cells in different forms, including topography, substrate stiffness, and geometrical constraint. With the recent advancement in microfabrication technology, researchers have gained the ability to manipulate the geometrical constraints by creating 3D structures to mimic the tissue microenvironment. In this study, we simulate the pore curvature as presented to the cells within 3D-engineered tissue-scaffolds by developing a device that features tortuous microchannels with geometric variations. We show that both cells at the front and rear respond to the varying radii of curvature and channel amplitude by altering the collective migratory behavior, including cell velocity, morphology, and turning angle. These findings provide insights into adaptive migration modes of collective cells to better understand the underlying mechanism of cell migration for optimization of the engineered tissue-scaffold design.

中文翻译：

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几何曲率对弯曲微通道装置中集体细胞迁移的影响。

集体细胞迁移是许多自然发生的病理生理过程以及组织工程应用中的重要现象。众所周知，组织和器官中的细胞能够感知来自微环境的化学和机械信号，并对这些信号做出集体反应。在过去的几十年里，在组织工程背景下，生长因子和治疗剂等化学信号对集体细胞行为的影响已被广泛研究，而机械信号的影响最近才被研究。机械信号可以以不同的形式呈现给组成细胞，包括形貌、基底刚度和几何约束。随着微加工技术的最新进展，研究人员已经能够通过创建 3D 结构来模拟组织微环境来操纵几何约束。在这项研究中，我们通过开发一种具有几何变化的曲折微通道的装置来模拟 3D 工程组织支架内细胞呈现的孔隙曲率。我们表明，前面和后面的细胞通过改变集体迁移行为（包括细胞速度、形态和转向角度）来响应不同的曲率半径和通道振幅。这些发现为集体细胞的适应性迁移模式提供了见解，以更好地了解细胞迁移的潜在机制，从而优化工程组织支架设计。