Cell-substrate distance fluctuations of confluent cells enable fast and coherent collective migration

Collective cell migration is an emergent phenomenon, with long-range cell-cell communication influenced by various factors, including transmission of forces, viscoelasticity of individual cells, substrate interactions, and mechanotransduction. We investigate how alterations in cell-substrate distance fluctuations, cell-substrate adhesion, and traction forces impact the average velocity and temporal-spatial correlation of confluent monolayers formed either by wild-type MDCKII cells or zonula occludens (ZO) 1/2-depleted MDCKII cells (dKD) representing highly contractile cells. The data indicates that confluent dKD monolayers exhibit decreased average velocity compared to less contractile WT cells concomitant with increased substrate adhesion, reduced traction forces, a more compact shape, diminished cell-cell interactions, and reduced cell-substrate distance fluctuations. Depletion of basal actin and myosin further supports the notion that short-range cell-substrate interactions, particularly fluctuations driven by basal actomyosin, significantly influence the migration speed of the monolayer on a larger length scale.