RT Journal Article SR Electronic T1 Myosin-II mediated traction forces evoke localized Piezo1 Ca2+ flickers JF bioRxiv FD Cold Spring Harbor Laboratory SP 294611 DO 10.1101/294611 A1 Kyle L. Ellefsen A1 Alice Chang A1 Jamison L. Nourse A1 Jesse R. Holt A1 Janahan Arulmoli A1 Armen Mekhdjian A1 Hamid Abuwarda A1 Francesco Tombola A1 Lisa A. Flanagan A1 Alexander R. Dunn A1 Ian Parker A1 Medha M. Pathak YR 2018 UL http://biorxiv.org/content/early/2018/10/12/294611.abstract AB Piezo channels transduce mechanical stimuli into electrical and chemical signals to powerfully influence development, homeostasis, and regeneration. Given their location in the plasma membrane, Piezo channels 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 internal, cell-generated forces vital for cellular and organismal physiology is poorly understood. Here, using direct measurements of endogenous Piezo1 activity and traction forces in native cellular conditions, we show that actomyosin-based cellular traction forces generate spatially-restricted Ca2+ flickers in the absence of dynamic, externally-applied mechanical forces. Although Piezo1 channels diffuse readily in the plasma membrane and are widely distributed across the cell, their flicker activity is enriched in regions proximal to force-producing adhesions. The mechanical force that activates Piezo1 arises from Myosin II phos-phorylation by Myosin Light Chain Kinase. We propose that Piezo1 Ca2+ flickers allow spatial segregation of mechanotransduction events, and that diffusion allows channel molecules to efficiently respond to transient, local mechanical stimuli.