DYNAMICS UNDERLYING TISSUE INTEGRITY

组织完整性的动力学

• 批准号: 8169585
• 负责人: Srinivas Ravi V Iyengar
• 金额: $ 1.63万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169585
• 关键词: Address; Binding; Cells; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Coupled; Devices; Disease; Endothelial Cells; Engineering; Filtration; Funding; Grant; Institution; Kidney; Life; Measures; Microfluidic Microchips; Modeling; Pharmaceutical Preparations; Process; Research; Research Personnel; Resources; Screening procedure; Signal Transduction; Source; Structure; System; Testing; Tissues; United States National Institutes of Health; autocrine; cell type; cellular imaging; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该项目旨在解决组织完整性的潜在机制。我们将组织视为相互作用的细胞和基质的网络。我们假设组织完整性是由不同细胞类型和将这些细胞结合在一起的基质之间的动态相互作用产生的信息整合产生的。为了检验这一假设，我们将重点关注肾脏肾小球滤过屏障。在该系统中，我们预测由足细胞、肾小球基底膜和内皮细胞组成的三节点环路之间的连续信息流会将这三个实体整合成一个单一的内聚功能结构：过滤屏障。这些信息既是化学的（分泌的自分泌/旁分泌因子以及细胞/细胞和细胞/基质接触）又是物理的（由细胞/细胞和细胞/基质接触产生的力）。来自物理和化学来源的信息通过足细胞和内皮细胞的细胞内信号网络无缝集成，以激发动态维持三节点环路的反应，从而实现组织的完整性和功能性。为了测试这些想法，我们将合并 3D 计算模型、纳米到微米级 3D 制造和纳米图案，耦合到微流体设备，以在工程设备内重建过滤屏障。我们将使用信号相互作用的活细胞成像来测量由重组组织组件之间的相互作用产生的信息流的动态，这些组件在设备内产生肾小球滤过屏障。预计这些研究将使我们能够确定组装功能组织的一般设计原则，从而有助于了解疾病过程和筛选新药。