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Key to collective cell migration is the ability of cells to rearrange their position with respect to their neighbors. Recent theory and experiments demonstrated that cellular rearrangements are facilitated by cell shape, with cells having more elongated shapes and greater perimeters more easily sliding past their neighbors within the cell layer. Though it is thought that cell perimeter is controlled primarily by cortical tension and adhesion at each cell's periphery, experimental testing of this hypothesis has produced conflicting results. Here we studied collective migration in an epithelial monolayer by measuring forces, cell perimeters, and motion, and found all three to decrease with either increased cell density or inhibition of cell contraction. In contrast to previous understanding, the data suggest that cell shape and rearrangements are controlled not by cortical tension or adhesion at the cell periphery but rather by the stress fibers that produce tractions at the cell-substrate interface. This finding is confirmed by an experiment showing that increasing tractions reverses the effect of density on cell shape and rearrangements. Our study therefore reduces the focus on the cell periphery by establishing cell-substrate traction as a major physical factor controlling shape and motion in collective cell migration.

Cells move in collective groups in biological processes such as wound healing, morphogenesis, and cancer metastasis. How active cell forces produce the motion in collective cell migration is still unclear. Many theoretical models have been introduced to elucidate the relationship between the cell's active forces and different observations about the collective motion such as collective swirls, oscillations, and rearrangements. though many models share the common feature of balancing forces in the cell layer, the specific relationships between force and motion vary among the different models, which can lead to different conclusions. Simultaneous experimental measurements of force and motion can aid in testing assumptions and predictions of the theoretical models. Here, we provide time-lapse images of cells in 1 mm circular islands, which are used to compute cell velocities, cell-substrate tractions, and monolayer stresses. Additional data are included from experiments that perturbed cell number density and actomyosin contractility. We expect this data set to be useful to researchers interested in force and motion in collective cell migration.

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.

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