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

• Published in: Cell reports (Cambridge) Vol. 43; no. 8; p. 114553
• Main Authors: Jipp, Marcel, Wagner, Bente D., Egbringhoff, Lisa, Teichmann, Andreas, Rübeling, Angela, Nieschwitz, Paul, Honigmann, Alf, Chizhik, Alexey, Oswald, Tabea A., Janshoff, Andreas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.08.2024; Elsevier
• Subjects: atomic force microscopy; cell mechanics; collective cell migration; CP: Cell biology; jamming; tight junctions; traction force microscopy; CP: Cell biology; jamming; cell mechanics; tight junctions; traction force microscopy; collective cell migration; atomic force microscopy
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114553

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 by either wild-type (WT) MDCKII cells or zonula occludens (ZO)-1/2-depleted MDCKII cells (double knockdown [dKD]) representing highly contractile cells. The data indicate 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. [Display omitted] •Active cell-substrate distance fluctuations are vital for pre-jamming motility•Basal actomyosin forces cause persistent cell-substrate distance fluctuations•Imbalanced basal/apical contractility disrupts ZO-1/2 KO cells’ coordinated motility Jipp et al. emphasize the significance of cell-substrate distance fluctuations together with adequate traction forces during collective monolayer motility, caused by basal contractility through actin stress fibers and myosin motors. Imbalances in apical and basal contractility in ZO-1/2 KO cells disrupt persistent, active shape fluctuations and therefore monolayer motility.