Unveiling mechanotransduction during collective cell migration

Collective cell migration (CCM) describes the coordinated movement and behavior of a group of cells. It relies heavily on cell-cell communication and microenvironmental interactions and is essential for embryonic morphogenesis, angiogenesis, wound repair and cancer invasion. CCM depends on physical forces applied directly onto adherent junctions (AJs). AJs are composed by a dynamic protein complex including core members of the cadherin and catenin families, and additional partners such as vinculin and actin regulators. Efficient mechanotransduction and collective polarization in CCM is directly dependent on the intricate connectivity between junctional proteins and the actin cytoskeleton. Although α-catenin is essential in cadherin-dependent mechanobiology, it remains unclear whether there are also α-catenin cadherin-independent functions in CCM. Moreover, despite the firm link between actin polymerization and mechanotransduction in CCM, little is known on the mechanisms recruiting and activating the Arp2/3 complex at AJs during CCM. In our lab, we established a method to evaluate cell coordination during CCM using front-rear polarity axis of groups of endothelial cells (ECs). We used this methodology to investigate α-catenin cadherin-independent functions and the mechanisms recruiting Arp2/3 complex at AJs in ECs undergoing CCM. We found that the role of α-catenin in CCM depends primarily on its binding to the cadherin complex, suggesting that cadherin-independent functions of α-catenin is absent in ECs. Additionally, we confirmed that Arp2/3 complex is essential for CCM and collective axial polarity. Mechanistically, we present initial evidences that Arp2/3 complex is recruited specifically to AJs by vinculin. Altogether, our work shows that cadherin-dependent mechanotransduction relies on Arp2/3 complex activity and highlights its function as novel regulator of axial polarity in ECs. Future insights on mechanobiology could provide new clues to design therapies to prevent cancer invasion