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: 9910693
• 负责人: Smiti Bhattacharya
• 金额: $ 4.5万
• 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/9910693
• 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; Image; Image Analysis; In Vitro; Injury; Integrin beta3; 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

项目总结