Cell Volume, Deformability & Dimensionability

项目摘要 在这个修改后的应用程序中，我们建议桥接生物学和物理学的前沿课题，以创建一个 肺健康和疾病中集体细胞迁移的新物理图像。这个项目和核心 该计划侧重于一个共同的中心假设：在肺上皮细胞的集体行为中， 玻璃的概念将各种物理因素及其多种生物效应结合在一起， 如在统一干扰相位图上所描述的过渡。每个项目总监都是其领域的领导者 各自的纪律。项目1（Weitz）将研究孤立的单细胞水平的基本物理学 (0-D)在单文件迁移（1-D）中，以及在向2-D行为的转换中。该项目将强调统一 细胞体积调节在细胞堵塞的机械决定因素中的作用。项目2（Fredberg）将调查 单分子层（2-D）和细胞簇（3-D）干扰的基本物理学。项目3（德拉赞）将调查 阻塞支气管上皮细胞的作用是哮喘发病的基本机制。核心A（Butler， Zaman，Krishnan）将支持和开发物理力成像的新技术。核心B（韦斯） 将寻找跨越项目和表征干扰阶段区域的共同分子网络基序 图表。核心C（Fredberg）是管理性的。总之，这个专业的跨学科项目和核心 GRAM项目将物理学和生物学联合收割机结合到了一个很少实现水平。这些项目由一个 核心假设是激进的，机械的和可检验的，并且有可能影响基本的， 肺损伤与修复。

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.