Regulation of collective cell polarity and migration using dynamically adhesive micropatterned substrates.

Abstract Collective cell migration is a fundamental biological process in which groups of cells move together in a coordinated manner, and it is essential for tissue development and wound repair. However, the underlying mechanisms that orchestrate directionality in collectively migrating cells remain poorly understood. In this study, we employed dynamically adhesive micropatterned substrates to investigate the role of adhesive cues in directing epithelial migration. Our findings demonstrate that epithelial cells collectively polarize in response to asymmetric patterns of extracellular matrix (ECM), and the degree of polarization depends on the degree of asymmetry and requires calcium-dependent cell-cell adhesion. When released from the micropatterns, epithelial cells collectively migrate according to the direction of pre-established polarity, and cohesive migration specifically requires E-cadherin-containing adherens junctions. Finally, disruption of the microtubule network blocks collective polarization and functionally inhibits directed migration. Together, these results indicate that adhesive cues from the ECM guide collective epithelial polarity and migration, and this response depends on adherens junctions and microtubules. Statement of significance This study employs a dynamically adhesive micropatterning platform to investigate the role of adhesive cues in directing the polarity and directional migration of epithelial cells. The findings demonstrate how asymmetric tissue geometry influences the collective directionality in simple epithelia and that this response is mediated by adherens junctions and the microtubule network. This work provides new insight into fundamental cellular processes involved in wound healing and has important implications for biomaterial and scaffold design.