Piezo1 Mobility Dynamics in Mechanotransduction

机械传导中的 Piezo1 移动动力学

基本信息

批准号：
10612807
负责人：
Alan Ly
金额：
$ 4.25万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10612807
关键词：
Acids Actins Actomyosin Affect Agonist Architecture Area Behavior Benzyl Alcohols Biological Process Biophysics Blood Vessels Cell Polarity Cell Shape Cell membrane Cells Characteristics Chemicals Cholesterol Cytoskeletal Modeling Cytoskeleton Data Defect Development Diffusion Embryo Environment Fibroblasts Fluorescence Microscopy Goals Human Image Imaging Techniques Ion Channel Ion Channel Gating Label Link Lipids Measurement Mechanics Membrane Membrane Proteins Molecular Mus Neurodegenerative Disorders Neurodevelopmental Disorder Pattern Physiological Physiological Processes Piezo 1 ion channel Play Process Proliferating Protein Dynamics Reporting Research Role Shapes Signal Transduction Skeletal Muscle System Testing Therapeutic Time Traction Work antagonist blood pressure regulation body system cell type experience experimental study gain of function mutation genetic manipulation human imaging induced pluripotent stem cell inhibitor insight ion dynamics mechanical force mechanical signal mechanotransduction migration nerve stem cell neural repair neurodevelopment non-invasive imaging novel particle pharmacologic polarized cell spatiotemporal stem cell fate transduction efficiency

项目摘要

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.

项目摘要/摘要：机械激活的离子通道 Piezo1 在各种生理过程中发挥着不同的作用，包括神经干/祖细胞的分化，然而，亚细胞扩散动力学。通道以及这些特征如何发挥其功能尚不清楚。单粒子跟踪分析表明 Piezo1 扩散受到细胞结构的影响（例如肌动蛋白细胞骨架和脂质环境）我们之前曾在方形细胞中报道过 Piezo1。鉴于 Piezo1 在高牵引力区域（边缘和顶点）的作用最为活跃。机械转导和神经发育，有必要了解 Piezo1 扩散在这些生物过程。我认为通道活动和细胞力学决定了 Piezo1 扩散动力学。对人类诱导多能性中的内源性 Piezo1 通道进行单粒子跟踪测量通过全内反射荧光显微镜观察干细胞衍生的神经干细胞 (hiPSC-NSC) （TIRFM）。我将在以下条件下对 Piezo1 扩散进行成像和分析：(1) Piezo1 活性具有药理学作用。 (ii) 细胞力学受到操纵。拟议的研究将阐明 Piezo1 扩散在力传导和弥合 Piezo1 活动和扩散之间的差距。