Mechanics of Monolayer Migration

单层迁移的力学

基本信息

批准号：
8645707
负责人：
Jeffrey J Fredberg
金额：
$ 60.59万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-06 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8645707
关键词：
Adhesions Adhesives Asthma Attention Biological Models Breathing Cell Adhesion Molecules Cell Communication Cell Line Cells Chemicals Chemotaxis Chronic Obstructive Airway Disease Coffee Complex Comprehension Data Duct (organ) structure Epithelial Event Fibrosis Functional disorder Goals Growth Heterogeneity Human Immigration Individual Lead Libraries Link Logic Lung Measures Mechanical Stress Mechanical ventilation Mechanics Mesenchymal Microscopy Molecular Morphogenesis Motion Natural regeneration Phase Physiology Play Population Preclinical Drug Evaluation Role Source Staging Stress Suggestion System Testing base bean body system cancer cell cell motility epithelial to mesenchymal transition injury and repair lung development men who have sex with men migration molecular scale monolayer new technology novel prototype public health relevance repaired research study stable cell line stem cell biology tumor progression

项目摘要

DESCRIPTION (provided by applicant): Cells in the lung often migrate not as individual entities but as collective sheets, ducts, strands, or clusters. But how each cell can coordinate its migration with that of immediate neighbors has defied full comprehension. We propose here the hypothesis that a much overlooked but nonetheless central feature of coordinated cellular migration is that each constituent cell can become physically constrained (jammed) by nearest neighbors. The jamming hypothesis is deceptively simple, yet makes mechanistic predictions a priori that are surprising, complex, and testable. It predicts: 1) that a cell within the integrated monolayer cannot migrate without cooperative motions of its immediate neighbors; 2) that this cooperativity retards system dynamics, and does so through spontaneous emergence of dramatically heterogeneous force chains that ripple through the system at multiple scales of organization; and 3) that decreasing adhesive interactions, or decreasing compressive stresses, or increasing tidal deformations as occur in breathing and mechanical ventilation, all serve to pro- mote cell unjamming and disaggregation, and are all described by a unified jamming phase diagram. Using a prototype of a unique experimental platform -Monolayer Stress Microscopy- we have obtained preliminary data supporting this novel physical picture. If it is shown to have predictive power, this hypothesis would bring together under one mechanistic rubric diverse aspects of collective sheet migrations in epithelial and endothelial monolayer physiology, as well as in repair, barrier function, fibrosis, and the epithelial-mesenchymal transition (EMT).

描述（由申请人提供）：肺中的细胞通常不是作为个体实体迁移，而是作为集体纸，管道，绞线或簇迁移。但是，每个细胞如何将其迁移与直接邻居的迁移保持不完全理解。我们在这里提出了这样一个假设，即协调的细胞迁移的众多但仍在的中心特征是，每个组成细胞都可以被最近的邻居受到物理限制（堵塞）。干扰假设在看似简单，但使机械预测成为令人惊讶，复杂且可检验的先验预测。它预测：1）综合单层中的细胞没有其直接邻居的合作动作就无法迁移； 2）这种合作性降低了系统动力学，并通过自发出现在多个组织的多个尺度上贯穿整个系统的自发出现； 3）降低粘合剂相互作用，减轻压缩应力，或增加呼吸和机械通气中发生的潮汐变形，所有这些都用于弥补细胞的不兼基和分解，并且都由统一的干扰相图来描述。使用独特的实验平台的原型 - 单层应力显微镜 - 我们获得了支持这种新型物理图片的初步数据。如果证明具有预测能力，则该假设将在上皮和内皮单层生理学中的集体片迁移的一个机械标题各种方面以及修复，屏障功能，纤维化和上皮 - 中层骨质质转变（EMT）中汇集在一起。