TY - JOUR T1 - Myosin-II mediated traction forces evoke localized Piezo1 Ca<sup>2+</sup> flickers JF - bioRxiv DO - 10.1101/294611 SP - 294611 AU - Kyle L. Ellefsen AU - Alice Chang AU - Jamison L. Nourse AU - Jesse R. Holt AU - Janahan Arulmoli AU - Armen Mekhdjian AU - Hamid Abuwarda AU - Francesco Tombola AU - Lisa A. Flanagan AU - Alexander R. Dunn AU - Ian Parker AU - Medha M. Pathak Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/10/12/294611.abstract N2 - 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. ER -