Department of Engineering Physics, University of Wisconsin-Madison, Madison, WI, USA.
Department of Mechanical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Sci Rep. 2022 Feb 15;12(1):2474. doi: 10.1038/s41598-022-06504-0.
In collective cell migration, the motion results from forces produced by each cell and transmitted to the neighboring cells and to the substrate. Because inertia is negligible and the migration occurs over long time scales, the cell layer exhibits viscous behavior, where force and motion are connected by an apparent friction that results from the breaking and forming of adhesive bonds at the cell-cell and cell-substrate interfaces. Most theoretical models for collective migration include an apparent friction to connect force and motion, with many models making predictions that depend on the ratio of cell-cell and cell-substrate friction. However, little is known about factors that affect friction, leaving predictions of many theoretical models untested. Here, we considered how substrate stiffness and the number of adhesions affected friction at the cell-substrate interface. The experimental data were interpreted through prior theoretical models, which led to the same conclusion, that increased substrate stiffness increased the number of cell-substrate adhesions and caused increased cell-substrate friction. In turn, the friction affected the collective migration by altering the curvature at the edge of the cell layer. By revealing underlying factors affecting friction and demonstrating how friction perturbs the collective migration, this work provides experimental evidence supporting prior theoretical models and motivates the study of other ways to alter the collective migration by changing friction.
在群体细胞迁移中,运动是由每个细胞产生的力,并传递到相邻细胞和基底上而产生的。由于惯性可以忽略,且迁移发生在很长的时间尺度上,细胞层表现出粘性行为,其中力和运动通过在细胞-细胞和细胞-基底界面处的粘合连接的断裂和形成而产生的表观摩擦力连接。大多数用于群体迁移的理论模型都包含一个表观摩擦力来连接力和运动,许多模型的预测取决于细胞-细胞和细胞-基底摩擦力的比值。然而,对于影响摩擦力的因素知之甚少,这使得许多理论模型的预测都未经检验。在这里,我们研究了基底刚度和黏附点数如何影响细胞-基底界面处的摩擦力。通过先前的理论模型对实验数据进行了解释,得出了相同的结论,即基底刚度的增加增加了细胞-基底黏附点数,并导致细胞-基底摩擦力增加。反过来,摩擦力通过改变细胞层边缘的曲率来影响群体迁移。通过揭示影响摩擦力的潜在因素,并展示摩擦力如何扰乱群体迁移,这项工作提供了支持先前理论模型的实验证据,并促使人们研究通过改变摩擦力来改变群体迁移的其他方法。