The stress of differentiation

Adherent cells balance adhesion to their substrate against contractile force acting on the cytoskeleton. But can tipping this balance affect a cell's fate? To find out, Dennis Discher and coworkers have examined how contractility affects the development of skeletal muscle myocytes (p. 5855). They culture myocytes on micropatterned slides containing thin rectangles of collagen substrate. This forces the myocytes to form linear rather than branched myotubes, which allows the authors to measure their contractility by seeing how much they shorten when one end is detached from the substrate. Interestingly, myotubes attached directly to the substrate do not differentiate properly, failing to generate the striations characteristic of skeletal muscle. By contrast, cells on top of this lower layer do become striated. Discher and co-workers correlate this with greater contractility of the upper-layer cells. They use an inhibitor of myosin II (blebbistatin) to show that this motor is the source of the contractile stress. The authors suggest that the more compliant adhesion the upper-layer cells experience (since they adhere to other cells not a rigid collagen substrate) leads to a difference in myosin-II-induced contractile stress that controls their ability to differentiate.