Hardin C Corey, Chattoraj Joyjit, Manomohan Greeshma, Colombo Jader, Nguyen Trong, Tambe Dhananjay, Fredberg Jeffrey J, Birukov Konstantin, Butler James P, Del Gado Emanuela, Krishnan Ramaswamy
Division of Pulmonary and Critical Care, Massachusetts General Hospital, Boston, MA, USA.
Department of Physics and Institute for Soft Matter Synthesis and Metrology, Georgetown University, Washington, DC, USA.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):749-754. doi: 10.1016/j.bbrc.2017.11.066. Epub 2017 Nov 11.
In endothelial gap formation, local tractions exerted by the cell upon its basal adhesions are thought to exceed balancing tensile stresses exerted across the cell-cell junction, thus causing the junction to rupture. To test this idea, we mapped evolving tractions, intercellular stresses, and corresponding growth of paracellular gaps in response to agonist challenge. Contrary to expectation, we found little to no relationship between local tensile stresses and gap formation. Instead, we discovered that intercellular stresses were aligned into striking multi-cellular domains punctuated by defects in stress alignment. Surprisingly, gaps emerged preferentially not at stress hotspots, as predicted, but rather at stress defects. This unexpected behavior is captured by a minimal model of the cell layer as a jammed assembly of cohesive particles undergoing plastic rearrangements under tension. Together, experiments and model suggest a new physical picture in which gap formation, and its consequent effect on endothelial permeability, is determined not by a local stress imbalance at a cell-cell junction but rather by emergence of non-local, cooperative stress reorganization across the cellular collective.
在内皮细胞间隙形成过程中，细胞对其基底黏附施加的局部牵引力被认为超过了跨细胞间连接施加的平衡拉伸应力，从而导致连接破裂。为了验证这一想法，我们绘制了在激动剂刺激下不断变化的牵引力、细胞间应力以及相应的细胞旁间隙生长情况。与预期相反，我们发现局部拉伸应力与间隙形成之间几乎没有关系。相反，我们发现细胞间应力排列成显著的多细胞区域，这些区域由应力排列缺陷打断。令人惊讶的是，间隙并非如预测的那样优先出现在应力热点处，而是出现在应力缺陷处。这种意外行为可以通过一个将细胞层视为在张力下经历塑性重排的粘性颗粒堵塞组件的简化模型来捕捉。实验和模型共同提出了一种新的物理图景，其中间隙形成及其对内皮通透性的后续影响不是由细胞间连接处的局部应力失衡决定的，而是由整个细胞群体中出现的非局部协同应力重组决定的。
