Contact inhibition of locomotion (CIL), in which cells repolarize and move away from contact, is now established as a fundamental driving force in development, repair, and disease biology. Much of what we know of CIL stems from studies on 2D substrates that fail to provide an essential biophysical cue - the curvature of extracellular matrix fibers. We discover rules controlling outcomes of cell-cell collisions on suspended nanofibers, and show them to be profoundly different from the stereotyped CIL behavior known on 2D substrates. Two approaching cells attached to a single fiber do not repolarize upon contact but rather usually migrate past one another. Fiber geometry modulates this behavior: when cells are attached to two fibers, reducing their freedom to reorient, only one of a pair of colliding cells repolarizes on contact, leading to the cell pair migrating as a single unit. CIL outcomes also change when one cell has recently divided and moves with high speed- cells more frequently walk past each other. In collisions with division in the two-fiber geometry, we also capture rare events where a daughter cell pushes the non-dividing cell along the fibers. Our computational model of CIL in fiber geometries reproduces the core qualitative results of the experiments robustly to model parameters. Our model shows that the increased speed of post-division cells may be sufficient to explain their increased walk-past rate. Our results suggest that characterizing cell-cell interactions on flat substrates, channels, or micropatterns is not sufficient to predict interactions in a matrix - the geometry of the fiber can generate entirely new behaviors.

中文翻译：

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悬浮纳米纤维上细胞运动的接触抑制规则

运动被抑制（CIL），其中细胞重新极化并远离接触，现已被确定为发展，修复和疾病生物学的基本驱动力。我们对CIL的大部分了解都来自对2D基质的研究，这些研究未能提供必要的生物物理线索-细胞外基质纤维的曲率。我们发现控制悬浮纳米纤维上细胞碰撞的结果的规则，并显示它们与2D基板上已知的定型CIL行为有很大不同。附着在一根纤维上的两个接近细胞在接触时不会重新极化，而是通常会相互迁移。纤维的几何形状会调节这种行为：当细胞附着在两条纤维上时，会降低其重新定向的自由度，一对碰撞细胞中只有一个会在接触时重新极化，导致细胞对迁移为一个单元。当一个单元最近分裂并以高速移动时，CIL结果也会发生变化-单元之间更频繁地走过彼此。在与两纤维几何形状的分裂碰撞中，我们还捕获了罕见事件，其中子细胞沿着纤维推动了非分裂细胞。我们在纤维几何形状中CIL的计算模型重现了实验的核心定性结果，可对参数进行建模。我们的模型表明，分割后单元格的增加速度可能足以解释其步行通过率。我们的结果表明，表征平坦基底，通道或微图案上的细胞间相互作用不足以预测基质中的相互作用-纤维的几何形状可以产生全新的行为。