Department of Mechanical Engineering, University of California, Santa Barbara, California, USA.
California NanoSystems Institute, University of California, Santa Barbara, California, USA.
Sci Rep. 2017 Aug 29;7(1):9720. doi: 10.1038/s41598-017-10069-8.
Collective cell migration plays a pivotal role in the formation of organs, tissue regeneration, wound healing and many disease processes, including cancer. Despite the considerable existing knowledge on the molecular control of cell movements, it is unclear how the different observed modes of collective migration, especially for small groups of cells, emerge from the known behaviors of individual cells. Here we derive a physical description of collective cellular movements from first principles, while accounting for known phenomenological cell behaviors, such as contact inhibition of locomotion and force-induced cell repolarization. We show that this theoretical description successfully describes the motion of groups of cells of arbitrary numbers, connecting single cell behaviors and parameters (e.g., adhesion and traction forces) to the collective migration of small groups of cells and the expansion of large cell colonies. Specifically, using a common framework, we explain how cells characterized by contact inhibition of locomotion can display coherent collective behavior when in groups, even in the absence of biochemical signaling. We find an optimal group size leading to maximal group persistence and show that cell proliferation prevents the buildup of intercellular forces within cell colonies, enabling their expansion.
细胞集体迁移在器官形成、组织再生、伤口愈合和许多疾病过程（包括癌症）中起着关键作用。尽管已经有相当多的关于细胞运动的分子控制的知识，但目前还不清楚不同的观察到的集体迁移模式，特别是对于小群体细胞，如何从单个细胞的已知行为中产生。在这里，我们从第一性原理出发，对集体细胞运动进行物理描述，同时考虑了已知的现象学细胞行为，例如运动抑制接触和力诱导的细胞重极化。我们表明，这种理论描述成功地描述了任意数量的细胞群体的运动，将单细胞行为和参数（例如，黏附力和牵引力）与小群体细胞的集体迁移和大细胞菌落的扩张联系起来。具体来说，我们使用一个通用框架解释了具有运动抑制接触特征的细胞如何在群体中表现出一致的集体行为，即使在没有生化信号的情况下也是如此。我们发现了一个最优的群体大小，使群体的持续时间最长，并表明细胞增殖可以防止细胞菌落中细胞间力的积累，从而使细胞菌落能够扩张。
