DYNAMICS UNDERLYING TISSUE INTEGRITY

组织完整性的动力学

• 批准号: 8362512
• 负责人: Srinivas Ravi V Iyengar
• 金额: $ 1.05万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362512
• 关键词: Address; Binding; Cells; Chemicals; Coupled; Devices; Disease; Endothelial Cells; Engineering; Filtration; Funding; Grant; Kidney; Life; Measures; Microfluidic Microchips; Modeling; National Center for Research Resources; Pharmaceutical Preparations; Principal Investigator; Process; Research; Research Infrastructure; Resources; Screening procedure; Signal Transduction; Source; Structure; System; Testing; Tissues; United States National Institutes of Health; autocrine; cell type; cellular imaging; cost; design; glomerular basement membrane; glomerular filtration; nano; nanopattern; paracrine; podocyte; reconstitution; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project seeks to address the mechanisms underlying tissue integrity. We view tissue as networks of interacting cells and matrices. We hypothesize that tissue integrity results from the integration of information that arises from the dynamic interactions between the different cell types and the matrices that bind these cells together. To test this hypothesis we will focus on the kidney glomerular filtration barrier. In this system we predict that continuous information flow between a three-node loop consisting of podocytes cells, glomerular basement membrane and endothelial cells results in integrating the three entities into a single cohesive functional structure: the filtration barrier. Such information is both chemical (secreted autocrine /paracrine factors and cell/cell and cell/matrix contacts) and physical (forces arising from cell/cell and cell/matrix contacts). The information from physical and chemical sources is seamlessly integrated by intracellular signaling networks in the podocytes and endothelial cells to evoke responses that dynamically sustain the three-node loop, resulting in tissue integrity and functionality. To test these ideas we will merge 3Dcomputational models, nano-to-micro scale 3D fabrication and nanopatterning coupled to microfluidic devices to reconstitute a filtration barrier within the engineered device. We will use live cell imaging of signaling interactions to measure the dynamics of information flow arising from interactions between components of the reassembled tissue that give rise to the glomerular filtration barrier within the device. It is anticipated that these studies will allow us to identify general design principles to assemble functional tissues that can aid in understanding disease processes and for screening for new drugs.

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