A model system to study mechanosensing in podocytes

项目总结 终末期肾病影响着数百万美国人，虽然在早期阶段可以通过 透析后，唯一的治疗方法是肾移植。足细胞与许多肾脏疾病有关。 它们在滤过屏障中的结构作用被认为是一个动态的过程，足细胞通过这个过程积极地 重组其肌动蛋白细胞骨架。这个项目的目标是将高内容的图像分析与一种新颖的 纳米技术平台，了解足细胞如何在受伤时保持其结构完整性，并利用这一点 研究主要细胞信号通路如何在肾小球环境中运行的系统。我们的新奇研究 平台由空间特定的微工程三维表面组成，可以诱导细胞-细胞的形成 以足细胞为单位的连接点。我们的平台允许研究足细胞生物力学以及其他生化 同时所有的特征都在生理上相关的微环境中。因此，该项目是 变革性在两个方面：第一，通过创建一个新的平台来研究足细胞生物学，具有更大的生理学 第二，应用该系统来测试改变的机械生物学的生物物理效应 可能在细胞水平上影响慢性肾脏疾病进展的信号。 1

PROJECT SUMMARY End stage renal disease affects millions of Americans and while manageable in its early phases through dialysis, the only treatment is kidney transplantation. Podocytes have been implicated in many kidney diseases and their structural role in the filtration barrier is thought to be a dynamic process by which the podocyte actively reorganizes its actin cytoskeleton. The goal of this project is to combine high-content image analysis with a novel nanotechnology platform to understand how podocytes retain their structural integrity against injury, and use this system to study how a major cell signaling pathway operates in the context of the glomerulus. Our novel research platform comprises spatially-specific microengineered 3-D surfaces that can induce the formation of cell-cell junctions in podocytes. Our platform allows the study of podocyte biomechanics along with other biochemical characteristics simultaneously all in a physiologically relevant microenvironment. Hence, the project is transformative in two ways: first by creating a new platform to study podocyte biology with greater physiological relevance and second by applying this system to test the biophysical effects of altered mechanobiological signaling that may affect the progression of chronic kidney disease at the cellular level. 1