ABSTRACT
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 mechanical forces in the environment as well as internal forces generated by cells. While much is known about how Piezo1 responds to externally-applied me-chanical 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 channel activity in human neural stem/progenitor cells and human fibroblasts are stimulated by proximal piconewton to nanonewton scale actomyosin-based cellular 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-mediated Ca2+ flickers allow spatial segregation of mechanotransduction events within cells, and that Piezo1 diffusion allows a few channel molecules to efficiently respond to transient and localized mechanical stimuli throughout the entire cell surface.
