Measurement of tissue viscosity to relate force and motion in collective cell migration

In tissue development, wound healing, and cancer invasion, coordinated cell motion arises from active forces produced by the cells. The relationship between force and motion remains unclear, however, because the forces are a sum active and passive contributions. Here, we show that the active forces can be decoupled from the passive by careful investigation of the distribution of shear stress against strain rate. With this method, we show experimentally that the order of magnitude of passive tissue viscosity is 100 Pa-hr and that increasing (decreasing) the actomyosin cytoskeleton and cell-cell adhesions increase (decrease) the magnitude of tissue viscosity. These results establish tissue viscosity as a meaningful way to describe the mechanical behavior of epithelial tissues, and demonstrate a direct relationship between tissue microstructure and material properties. By providing the first experimental measurement of tissue viscosity, our study separates the active and passive components of stress, in turn clarifying the relationship between force and motion and providing a new means of identifying how active cell forces evolve in space and time.