Abstract
Cell adhesion to the substratum and/or other cells is a crucial step of cell migration. While essential in the case of solitary migrating cells (for example, immune cells), it becomes particularly important in collective cell migration, in which cells maintain contact with their neighbors while moving directionally. Adhesive coordination is paramount in physiological contexts (for example, during organogenesis) but also in pathology (for example, tumor metastasis). In this review, we address the need for a coordinated regulation of cell-cell and cell-matrix adhesions during collective cell migration. We emphasize the role of the actin cytoskeleton as an intracellular integrator of cadherin- and integrin-based adhesions and the emerging role of mechanics in the maintenance, reinforcement, and turnover of adhesive contacts. Recent advances in understanding the mechanical regulation of several components of cadherin and integrin adhesions allow us to revisit the adhesive clutch hypothesis that controls the degree of adhesive engagement during protrusion. Finally, we provide a brief overview of the major impact of these discoveries when using more physiological three-dimensional models of single and collective cell migration.
Highlights
Adhesion is a fundamental cellular property that shapes the architecture of complex, multicellular tissues and enables their maintenance
Toward an integrated model of dynamic cell-cell and cell-matrix adhesion to coordinate collective cell migration Throughout this review, we have described adhesive complexes that mediate stable interactions between cells and other cells as well as complexes that assemble and disassemble dynamically
Concluding remarks The vast amount of knowledge amassed over the last 40 years has yielded a detailed description of the molecular players involved in cell-cell and cell-matrix adhesions
Summary
Adhesion is a fundamental cellular property that shapes the architecture of complex, multicellular tissues and enables their maintenance. Unlike cadherin-based contacts, cell-matrix adhesions turn over frequently and form again to permit cell movement when a migratory requirement emerges This is controlled through the conformational activation of integrins. If the contact with the monolayer is not broken, these cells become “leaders” and propel the migration of the entire cohort toward the migratory cue In this scenario, efficient coordination between cadherin- and integrin-dependent adhesive complexes is required for collective migration. The (relatively) novel discovery of the mechanical regulation of adhesive adaptors and their coupling to the actin cytoskeleton represent a tunable link in a continuous, mechanically active chain that connects extracellular properties to intracellular responses These include morphological, transcriptional, and translational cell and tissue adaptations to the microenvironment. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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