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，而是作为集合片、导管、线或簇迁移。但每个细胞如何协调其与邻近细胞的迁移仍然无法完全理解。我们在这里提出一个假设，即协调细胞迁移的一个被忽视但仍然重要的特征是每个组成细胞都可能受到最近邻居的物理约束（堵塞）。干扰假说看似简单，但却做出了令人惊讶、复杂且可测试的先验机械预测。它预测：1）集成单层内的细胞如果没有其直接邻居的协作运动就无法迁移； 2）这种协作性阻碍了系统的动态，并且是通过自发出现的显着异质的力链来实现的，这些力链在组织的多个尺度上波及系统； 3）减少粘附相互作用，或减少压缩应力，或增加呼吸和机械通气中发生的潮汐变形，所有这些都有助于促进细胞解干扰和解聚，并且都由统一的干扰相图来描述。使用独特的实验平台原型——单层应力显微镜——我们获得了支持这一新颖物理图片的初步数据。如果它被证明具有预测能力，那么这一假设将把上皮和内皮单层生理学以及修复、屏障功能、纤维化和上皮-间质转化（EMT）中集体片迁移的不同方面汇集在一个机制标题下。）。