Piezo1 activation gains traction

Abstract

A major unanswered question in biology is how mechanical forces are generated, detected and transduced by cells to impact biochemical and genetic programs. Our work is aimed at uncovering the mechanical principles at play in cells and tissues using novel molecular, imaging and bioengineering tools. Here we present insights gleaned from non‐invasive approaches to measure and manipulate mechanical signals in native cellular conditions. We find that the mechanically‐activated ion channel Piezo1 transduces cell‐generated traction forces to regulate lineage choice of neural stem cells. We show that actomyosin‐based cellular traction forces generate spatially‐restricted Piezo1 Ca2+ flickers in the absence of externally‐applied mechanical forces. Although Piezo1 channels diffuse readily in the plasma membrane and are widely distributed across the cell, their Ca2+ flicker activity is enriched in regions proximal to force‐producing adhesions. The mechanical force that activates Piezo1 arises from Myosin II phosphorylation by Myosin Light Chain Kinase. We propose that Piezo1 Ca2+ flickers allow spatial segregation of mechanotransduction events, and that mobility allows channel molecules to efficiently respond to local mechanical stimuli.Support or Funding InformationNIH grants R01 NS109810 and DP2 AT010376