Piezo1 Mobility Dynamics in Mechanotransduction

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Project Summary/Abstract: The mechanically-activated ion channel Piezo1 plays diverse roles in various physiological processes, including the differentiation of neural stem/progenitor cells. However, the subcellular diffusion dynamics of the channel, and how these characteristics contribute to its function, are unknown. Single-particle tracking analysis suggests that Piezo1 diffusion is affected by cellular architecture (e.g. actin cytoskeleton and the lipid environment). We have previously reported in square-shaped cells that Piezo1 is most active in high traction force regions (edges and vertices). Given Piezo1’s diverse role in mechanotransduction and neurodevelopment, it is necessary to understand the role of Piezo1 diffusion in these biological processes. I hypothesize that channel activity and cellular mechanics determine Piezo1 diffusion dynamics. I will perform single-particle tracking measurements of endogenous Piezo1 channels in human induced pluripotent stem cell-derived neural stem cells (hiPSC-NSCs) via Total Internal Reflection Fluorescence microscopy (TIRFM). I will image and analyze Piezo1 diffusion in conditions where (1) Piezo1 activity is pharmacologically and genetically manipulated and (ii) cellular mechanics is manipulated . The proposed research will elucidate the function of Piezo1’s diffusion in mechanotransduction and bridge the gap between Piezo1 activity and diffusion.