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 Piezo1 responds to external forces, its response to cell-generated forces that are vital for cellular and organismal physiology is poorly understood. Here we show that Ca2+ flickers generated by endogenous Piezo1 in human neural stem cells and in fibroblasts are stimulated by actomyosin-based traction forces. Further, although Piezo1 channels diffuse readily in the plasma membrane and are widely distributed across the cell, flicker activity is enriched in spatially constrained regions at force-producing adhesions. We propose that Piezo1 Ca2+ flickers allow spatial segregation of mechanotransduction events, and that Piezo1 diffusion allows channel molecules to efficiently respond to transient and localized mechanical stimuli throughout the cell surface.