Relationship between cell force, shape, and motion in collective cell migration

In biological tissues, collective cell groups exhibit a transition from a solid-like state, wherein cell positions remain fixed, to a fluid-like state, wherein cells flow freely and rearrange their positions with their neighbors. Recent theoretical models and experiments have demonstrated that this transition can be predicted by average cell shape, with cells having more elongated shapes and greater perimeters more easily sliding past their neighbors. Cell perimeter is hypothesized to be controlled by the cell surface tension which is an interplay of the cell’s cortical actomyosin contractility and cell-cell adhesions. However, the hypothesis is still experimentally unexplored. Here, we investigate the factors affecting cell perimeter, and we quantify the corresponding effects on collective migration. For this, we perturb actin and myosin-II in epithelial (MDCK) cell monolayers and study the effects on force, shape, and motion. We employ traction force microscopy, fluorescent imaging, and quantitative image analysis to measure forces, cell perimeters, and migration respectively. By combining these experimental measurements, our study provides experimental testing of the theoretical models and establishes new principles relating cell force, shape, and motion.