Collective Mechanical Signaling Through Cell-Cell Contacts

The coordinated movement of epithelial cells known as collective migration is a key feature of epithelia development and repair. Mechanical linker proteins between cells such as those interacting with the cadherins complex are critical in regulating collective migration, as intercellular forces on these proteins activate downstream signals influencing cell function. Unfortunately, the way in which local mechanical signals propagate through epithelia to influence collective cellular migration is not well understood. Therefore, our lab has developed a series of microfabricated tools and quantitative approaches to both apply and measure different modes of mechanical strain on epithelial cell-cell contacts to determine their impact on epithelial behavior. In vitro, we have recently demonstrated local mid-plane epithelia shear perturbation to induce specific modes of collective, global epithelial migration dependent on intact intercellular cadherin and actomyosin signaling. In our work we have conducted a single-cell level spatiotemporal analysis of how local mechanical shear propagates change in cell morphology throughout an epithelium. These results provide the framework for biophysical models of global epithelial migration patterns. Furthermore, we have combined micromanipulation tools with a linear micropatterned epithelial model to dissect the role of single cell level intercellular cues on cell migration. Ultimately, our work combines experimental and quantitative analytical approaches to uncover the intercellular mechanics governing epithelial cell migration.