Cell Volume, Deformability & Dimensionability

细胞体积、变形能力

• 批准号: 9086402
• 负责人: DAVID A WEITZ
• 金额: $ 48.42万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9086402
• 关键词: 3-Dimensional; Asthma; Behavior; Biological; Biology; Bronchial Spasm; CREB1 gene; Candidate Disease Gene; Cell Volumes; Cells; D Cells; Discipline; Disease; Epithelial Cells; Genomics; Glass; Health; Human; Image; Imaging technology; Laboratories; Lung; Lung diseases; MDCK cell; Mechanics; Methodology; Methods; Molecular; Pathogenesis; Phase; Phenotype; Physics; Process; Regulation; Role; Signal Pathway; Stress; System; Wound Healing; activating transcription factor 3; airway epithelium; asthmatic; bronchial epithelium; cell motility; lung injury; lung repair; migration; monolayer; new technology; novel; programs; response; transmission process

PROJECT ABSTRACT In this revised application we propose to bridge cutting-edge topics in biology and physics in order to create a new physical picture of collective cellular migration in lung health and disease. The projects and cores of this program focus upon a common central hypothesis: In collective behaviors of epithelial cells in the lung, di- verse physical factors and their multiple biological effects are brought together by the concept of the glass transition as described on a unifying jamming phase diagram. Each project director is a leader in his or her respective discipline. Project 1 (Weitz) will investigate basic physics at the level of the single cell in isolation (0-D), in single-file migration (1-D), and in transition to 2-D behavior. This project will emphasize the unifying role of cell volume regulation in mechanical determinants of cell jamming. Project 2 (Fredberg) will investigate basic physics of jamming in monolayers (2-D) and cell clusters (3-D). Project 3 (Drazen) will investigate the role of jamming in the bronchial epithelium as a basic mechanisms of asthma pathogenesis. Core A (Butler, Zaman, Krishnan) will support and develop novel technologies for imaging of physical forces. Core B (Weiss) will seek common molecular network motifs that span projects and characterize regions of the jamming phase diagram. Core C (Fredberg) is administrative. Together, the interdisciplinary projects and cores of this pro- gram project combine physics and biology at a level that is realized only rarely. The projects are unified by a central hypothesis that is radical, mechanistic and testable, and that has the potential to impact basic under- standing of lung injury and repair.

项目摘要 在这个修订的应用程序中，我们建议在生物学和物理学的前沿主题之间架起桥梁，以便创建一个 肺部健康和疾病中细胞集体迁移的新物理图景。它的项目和核心 程序集中于一个共同的中心假设：在肺上皮细胞的集体行为中， 玻璃的概念将物理因素及其多重生物效应结合在一起 如统一干扰相图中所述的过渡。每个项目总监都是他或她的领导者 各自的纪律。项目1(魏茨)将在孤立的单个细胞水平上研究基础物理 (0-D)、单文件迁移(1-D)以及过渡到2-D行为。本项目将强调统一 细胞体积调节在细胞干扰的机械决定因素中的作用。项目2(Fredberg)将调查 单层(2-D)和细胞团(3-D)中干扰的基本物理学。项目3(德拉赞)将调查 支气管上皮堵塞是哮喘发病的基本机制之一。核心A(巴特勒， Zaman，Krishnan)将支持和开发物理力量成像的新技术。核心B(Weiss) 将寻找跨越项目和表征干扰阶段区域的共同分子网络基元 图表。核心C(Fredberg)是行政管理部门。总而言之，该专业的跨学科项目和核心- GRAM项目将物理学和生物学结合在一起，达到了很少有人实现的水平。这些项目由一个 中心假说是激进的、机械论的和可检验的，并有可能影响基本的欠 肺损伤与修复的现状。