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Peyret, G.

Publications and source records attributed to Peyret, G..

2 recordsLinked to original sources

Sustained oscillations of epithelial cell sheets

Morphological changes during development, tissue repair, and disease largely rely on coordinated cell movements and are controlled by the tissue environment. Epithelial cell sheets are often subjected to large scale deformation during tissue formation. The active mechanical environment in which epithelial cells operate have the ability to promote collective oscillations, but how these cellular movements are generated and relate to collective migration remains unclear. Here, combining in vitro experiments and computational modelling we describe a novel mode of collective oscillations in confined epithelial tissues where the oscillatory motion is the dominant contribution to the cellular movements. We show that epithelial cells exhibit large-scale coherent oscillations when constrained within micro-patterns of varying shapes and sizes, and that their period and amplitude are set by the smallest confinement dimension. Using molecular perturbations, we then demonstrate that force transmission at cell-cell junctions and its coupling to cell polarity are pivotal for the generation of these collective movements. We find that the resulting tissue deformations are sufficient to trigger mechanotransduction within cells, potentially affecting a wide range of cellular processes.

biophysics↗

Force-Dependent Binding Of Vinculin To α-Catenin Regulates Cell-Cell Contacts Stability And Collective Cell Behavior

The shaping of a multicellular body and repair of adult tissues require fine-tuning of cell adhesion, cell mechanics and intercellular transmission of mechanical load. Adherens junctions (AJs) are the major intercellular junctions by which cells sense and exert mechanical force on each other. However, how AJs adapt to mechanical stress and how this adaptation contributes to cell-cell cohesion and eventually to tissue-scale dynamics and mechanics remains largely unknown. Here, by analyzing the tension-dependent recruitment of vinculin, -catenin and F-actin as a function of stiffness, as well as the dynamics of GFP-tagged wild-type and mutated -catenins, altered for their binding capability to vinculin, we demonstrate that the force-dependent binding of vinculin stabilizes -catenin and is responsible for AJ adaptation to force. Challenging cadherin complexes mechanical coupling with magnetic tweezers, and cell-cell cohesion during collective cell movements, further highlight that tension-dependent adaptation of AJs regulates cell-cell contact dynamics and coordinated collective cell migration. Altogether, these data demonstrate that the force-dependent -catenin/vinculin interaction, manipulated here by mutagenesis and mechanical control, is a core regulator of AJ mechanics and long-range cell-cell interactions.\n\nSummary statementCombining cell biology and biomechanical analysis, we show here that the coupling between cadherin complexes and actin trough tension-dependent -catenin/vinculin association is regulating AJ stability and dynamics as well as tissue-scale mechanics.

cell biology↗