Piezo1 balances membrane and cortex tension to stabilize intercellular junctions and maintain the epithelial barrier

Formation of the skin barrier is essential for organismal survival and tissue homeostasis. Barrier formation requires positioning of functional tight junctions (TJs) to the most suprabasal viable layer of the epidermis through a mechanical circuit that is driven by generation of high tension at adherens junctions. However, what allows the sensing of tension build-up at these adhesions and how this tension is balanced to match the requirements of tissue mechanical properties is unclear. Here, we show that the mechanosensitive ion channel Piezo1 is essential for the maturation of intercellular junctions into functional continuous adhesions. Deletion of Piezo1 results in an imbalance of cell contractility and membrane tension, leading to a delay in adhesion maturation. Consequently, the requirement for Piezo1 activity can be bypassed by lowering contractility or elevating membrane tension. In vivo, Piezo1 function in adhesion integrity becomes essential only in aged mice where alterations in tissue mechanics lead to impaired tight junctions and barrier dysfunction. Collectively these studies reveal an essential function of Piezo1 in the timely establishment and maintenance of cell-cell junctions within a mechanically tensed epidermis.