Piezo1 calcium flickers localize to hotspots of cellular traction forces

Piezo channels transduce mechanical stimuli into electrical and chemical signals to powerfully influence development, homeostasis, and regeneration. Due to their location in the plasma membrane, they are positioned to transduce both external forces and internal forces generated by cells. While much is known about how Piezo1responds to external forces, its response to cell- generated forcesthat are vital for cellular and organismal physiology is poorly understood. Here we show that Ca2+ flickersgenerated by endogenous Piezo1in human neural stem cellsand in fibroblasts are stimulated by actomyosin-based traction forces. Further, although Piezo1channels diffuse readily in the plasma membrane and are widely distributed across the cell, flickeractivity is enriched in spatially constrained regions at force-producing adhesions. We propose that Piezo1Ca2+ flickersallow spatial segregation of mechanotransductionevents, and that Piezo1diffusion allows channel molecules to efficiently respond to transient and localized mechanical stimuli throughout the cell surface.