Coordination of contractile tension and cell area changes in an epithelial cell monolayer

During tissue development and repair, cells contract and expand in coordination with their neighbors, giving rise to tissue deformations that occur on length scales far larger than that of a single cell. The biophysical mechanisms by which the contractile forces of each cell cause deformations on multicellular length scales are not fully clear. To investigate this question, we began with the principle of force equilibrium, which dictates a balance of tensile forces between neighboring cells. Based on this principle, we hypothesized that coordinated changes in cell area result from tension transmitted across the cell layer. To test this hypothesis, spatial correlations of both contractile tension and the divergence of cell velocities were measured as readouts of coordinated contractility and collective area changes, respectively. Experiments were designed to alter the spatial correlation of contractile tension using three different methods, including disrupting cell-cell adhesions, modulating the alignment of actomyosin stress fibers between neighboring cells, and changing the size of the cell monolayer. In all experiments, the spatial correlations of both tension and divergence increased or decreased together, in agreement with our hypothesis. To relate our findings to the intracellular mechanism connecting changes in cell area to contractile tension, we disrupted activation of extracellular signal-regulated kinase (ERK), which is known to mediate the intracellular relationship between cell area and contraction. Consistent with prior knowledge, a temporal cross-correlation between cell area and tension revealed that ERK was responsible for a proportional relationship between cell area and contraction. Inhibition of ERK activation reduced the spatial correlations of the divergence of cell velocity but not of tension. Together, our findings suggest that coordination of cell contraction and expansion requires transfer of cell tension over space and ERK-mediated coordination between cell area and contraction in time.