The epithelium is subjected to multiple types of mechanical stretch. Researchers have discovered that the proteins ZO-1 and ZO-2, which contribute to the tightness of the epithelium, perceive these physical signals and activate cellular responses accordingly. These results reveal a novel process by which mechanical forces can regulate the structure of epithelia, their dynamic equilibrium and the establishment of tissue barriers. Targeted inhibition of ZO-1 in tumors could therefore be a pathway to explore.