Directed cell migration following the gradients of extracellular matrix stiffness, termed durotaxis, plays an essential role in development, wound healing, and cancer invasion. Here, we develop a cytoskeleton-based mechanical model to study the migration modes of both isolated cells and cell clusters on gradient substrates. We find that collective cell durotaxis is attributed to the geometrical restriction of cell rotation by neighboring cells, leading to a different migration mode from isolated cells. Moreover, isolated cells are able to undergo directed migration on a soft substrate with relatively high stiffness gradients. In addition, collective cell durotaxis is far more efficient than single-cell durotaxis. The migration mode is determined by the competition between the difference of traction forces between the cell-substrate interface and the random force from microenvironments. This study indicates that isolated cells are more sensitive to environmental fluctuations, whereas cell clusters can counteract the effects of fluctuations by cell–cell interactions.

中文翻译：

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旋转约束有助于集体细胞旋转

定向的细胞迁移遵循称为durotaxis的细胞外基质刚度的梯度，在发育，伤口愈合和癌症侵袭中起重要作用。在这里，我们建立了一个基于细胞骨架的力学模型，以研究分离的细胞和细胞团簇在梯度基质上的迁移模式。我们发现集体细胞durotaxis归因于相邻细胞的细胞旋转的几何限制，从而导致与孤立细胞不同的迁移模式。而且，分离的细胞能够以较高的刚度梯度在软质基底上进行定向迁移。另外，集体细胞durotaxis比单细胞durotaxis效率更高。迁移模式由细胞-底物界面之间的牵引力之差与微环境的随机力之间的竞争决定。这项研究表明，分离的细胞对环境波动更敏感，而细胞簇可以通过细胞间相互作用来抵消波动的影响。