Milk production by the mammary epithelium relies on the coordinated action of luminal milk-producing cells and basal milk-ejecting cells, which contract in response to the hormone oxytocin. While the chemical signals that orchestrate lactation, and later the removal of mammary epithelial cells during involution are well understood, the role of mechanical forces in these processes remains open to investigation. Now, Felicity Davis and colleagues (Stewart et al., 2021) characterise forces experienced by mammary epithelial cells during and after the lactation period. 3D time-lapse imaging of mammary tissue from lactating mice before and following oxytocin stimulation revealed stochastic cell shape changes resulting from repetitive basal cell contractions. Assessing cell shape and surface characteristics from lactation to mammary gland involution, the authors report that the intraluminal pressure during involution is absorbed by the apical cell membrane of luminal cells. Then, to better understand the basis of force sensing, the authors perform in vitro lactogenic differentiation assays and intracellular Ca2+ measurements and show that epithelial cells respond to fluid shear stress. Finally, gene expression analysis revealed that Piezo1 is the only mechanically activated ion channel displaying increased expression during lactation; however, conditional deletion of Piezo1 in luminal cells did not affect lactation or involution in mice. Together, this work provides new insights into the mechanobiology of the mammary gland and invites further investigation into the role of PIEZO1 in this context.
