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 终末期肾病影响着数百万美国人，虽然在其早期阶段可以通过 透析，唯一的治疗方法是肾移植。足细胞与许多肾脏疾病有关 它们在过滤屏障中的结构作用被认为是一个动态过程，足细胞通过该过程积极地 重组其肌动蛋白细胞骨架。这个项目的目标是将联合收割机高内涵的图像分析与一个新的 纳米技术平台，以了解足细胞如何保持其结构完整性，以防止损伤，并使用这种 系统研究一个主要的细胞信号通路如何在肾小球的背景下运作。我们的新研究 该平台包括空间特异性微工程化的3-D表面，其可以诱导细胞-细胞微结构的形成。 足细胞中的连接。我们的平台允许研究足细胞生物力学沿着其他生化 所有这些都是在生理相关的微环境中同时进行的。因此，该项目是 在两个方面具有变革性：首先，通过创建一个新的平台来研究足细胞生物学， 第二，通过应用该系统来测试改变的机械生物学的生物物理效应， 在细胞水平上可能影响慢性肾病进展的信号传导。 1