Mechanics of Monolayer Migration

描述（由申请人提供）：肺中的细胞通常不是作为单个实体迁移，而是作为集合片、导管、束或簇迁移。但是，每个细胞如何协调其与近邻细胞的迁移，还没有完全理解。我们在这里提出的假设，一个被忽视的，但协调细胞迁移的中心特征是，每个组成细胞可以成为物理约束（堵塞）最近的邻居。干扰假说看似简单，但它的先验机制预测却令人惊讶、复杂且可检验。它预测：1）在整合单层内的细胞不能在没有其紧邻的细胞的合作运动的情况下迁移; 2）这种合作性阻碍了系统动力学，并且通过自发出现在多个组织尺度上涟漪通过系统的显著异质力链来实现;和3）减少粘附相互作用，或减少压缩应力，或增加在呼吸和机械通气中发生的潮汐变形，都用于促进小区解除干扰和分解，并且都由统一的干扰相位图描述。使用一个独特的实验平台的原型-单层应力显微镜-我们已经获得了支持这一新的物理图像的初步数据。如果它被证明具有预测能力，这种假设将汇集在一个机制的标题下，在上皮和内皮细胞单层生理学，以及在修复，屏障功能，纤维化，和上皮-间充质转化（EMT）的集体片迁移的各个方面。

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).