Mechanical waves during tissue expansion

\u3cp\u3eThe processes by which an organism develops its shape and heals wounds involve expansion of a monolayer sheet of cells. The mechanism underpinning this epithelial expansion remains obscure, despite the fact that its failure is known to contribute to several diseases, including carcinomas, which account for about 90% of all human cancers. Here, using the micropatterned epithelial monolayer as a model system, we report the discovery of a mechanical wave that propagates slowly to span the monolayer, traverses intercellular junctions in a cooperative manner and builds up differentials of mechanical stress. Essential features of this wave generation and propagation are captured by a minimal model based on sequential fronts of cytoskeletal reinforcement and fluidization. These findings establish a mechanism of long-range cell guidance, symmetry breaking and pattern formation during monolayer expansion.\u3c/p\u3

Control of cell–cell forces and collective cell dynamics by the intercellular adhesome

Dynamics of epithelial tissues determine key processes in development, tissue healing and cancer invasion. These processes are critically influenced by cell-cell adhesion forces. However, the identity of the proteins that resist and transmit forces at cell-cell junctions remains unclear, and how these proteins control tissue dynamics is largely unknown. Here we provide a systematic study of the interplay between cell-cell adhesion proteins, intercellular forces and epithelial tissue dynamics. We show that collective cellular responses to selective perturbations of the intercellular adhesome conform to three mechanical phenotypes. These phenotypes are controlled by different molecular modules and characterized by distinct relationships between cellular kinematics and intercellular forces. We show that these forces and their rates can be predicted by the concentrations of cadherins and catenins. Unexpectedly, we identified different mechanical roles for P-cadherin and E-cadherin; whereas P-cadherin predicts levels of intercellular force, E-cadherin predicts the rate at which intercellular force builds up.Peer ReviewedPostprint (published version