A model system to study mechanosensing in podocytes

研究足细胞机械传感的模型系统

• 批准号: 10017024
• 负责人: Smiti Bhattacharya
• 金额: $ 4.55万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-06 至 2021-09-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017024
• 关键词: 3-Dimensional; Actins; Affect; American; Architecture; Atomic Force Microscopy; Binding; Biochemical; Biological Models; Biology; Biomechanics; Biomimetics; Biophysics; Biosensor; Cell Communication; Cell Culture Techniques; Cell Nucleus; Cell Shape; Cells; Cellular Structures; Cellular biology; Characteristics; Chronic Kidney Failure; Cues; Cytoplasm; Cytoskeleton; D Cells; Dialysis procedure; Disease; Drug Targeting; Elasticity; End stage renal failure; Engineering; Environment; Exhibits; F-Actin; Fellowship; Fiber; Filtration; Focal Adhesions; Foot Process; Genes; Genetic Transcription; Goals; Growth; Heterogeneity; Human; ITGB3 gene; Image; Image Analysis; In Vitro; Injury; Integrins; Intercellular Junctions; Kidney; Kidney Diseases; Kidney Failure; Kidney Transplantation; Maintenance; Measures; Mechanics; Mediating; Migration Assay; Morphology; Mutate; NPHS2 protein; Nuclear; Pathway interactions; Peripheral; Pharmaceutical Preparations; Phase; Phenotype; Physiological; Physiology; Play; Process; Production; Property; Proteins; Renal glomerular disease; Reproducibility; Research; Role; Shapes; Signal Pathway; Signal Transduction; Signaling Protein; Site; Structure; Study models; Surface; System; Techniques; Testing; Translating; Up-Regulation; Vinculin; base; biochip; cell growth; cell motility; cellular transduction; design; experience; imaging study; improved; in vivo; innovation; kidney cell; mechanotransduction; mutant; nanotechnology platform; nephrin; nephrotoxicity; novel; podocyte; polarized cell; pre-doctoral; preservation; protein crosslink; quantitative imaging; resilience; response; segregation; slit diaphragm; tissue culture; training opportunity

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

项目摘要 末期肾脏疾病会影响数百万的美国人，虽然可以通过 透析，唯一的治疗方法是肾脏移植。足细胞与许多肾脏疾病有关 它们在过滤屏障中的结构作用被认为是一个动态的过程 重组其肌动蛋白细胞骨架。该项目的目的是将高含量图像分析与新颖 纳米技术平台，以了解足细胞如何保留其结构性完整性，并使用它 研究主要细胞信号通路在肾小球背景下如何运行的系统。我们的新研究 平台包括空间特异性的微工程3-D表面，可以诱导细胞细胞的形成 足细胞的连接。我们的平台允许研究足细胞生物力学以及其他生化 在生理相关的微环境中同时的特征。因此，该项目是 通过两种方式进行变革：首先，通过创建一个新的平台来研究Podocyte生物学，具有更大的生理学 相关性，其次是应用该系统测试改变机械生物学的生物物理效应 可能影响细胞水平慢性肾脏疾病进展的信号传导。 1