Mechanical tugging force regulates the size of cell-cell junctions
Mechanical tugging force regulates the size of cell-cell junctions
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DOI：
10.1073/pnas.0914547107
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发表时间：
2010-06-01
影响因子：
11.1
通讯作者：
Chen, Christopher S.
中科院分区：
文献类型：
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作者：
Liu, Zhijun;Tan, John L.;Chen, Christopher S.
肌动球蛋白的收缩性部分通过在细胞-基质和细胞-细胞接触部位产生机械力来影响组织内的细胞组织。虽然增加细胞-基质粘附的机械负荷导致局灶性粘附生长，但力是否驱动细胞-细胞粘附大小的变化仍然是一个悬而未决的问题。为了研究粘附连接（AJ）对力的响应性，我们采用了一种微制造力传感器系统来定量报告细胞-细胞牵引力和AJ大小。我们观察到AJ的大小受到内皮细胞-细胞牵引力的调节：AJs和牵引力分别随着肌球蛋白的激活或抑制而增加或减少。肌凝蛋白依赖的AJs调控与Rac1协同工作，这种协调调节通过血管渗透性药物（S1P，凝血酶）对连接稳定性的影响通过改变这些药物与Rac和肌凝蛋白依赖途径的耦合程度而被逆转。此外，直接施加机械拉力，而不是肌球蛋白活性本身，足以触发AJ生长。这些发现表明，机械力和细胞-细胞粘附相互作用的动态协调可能对维持多细胞完整性至关重要，并强调需要新的方法来研究拖曳力。
Actomyosin contractility affects cellular organization within tissues in part through the generation of mechanical forces at sites of cell-matrix and cell-cell contact. While increased mechanical loading at cell-matrix adhesions results in focal adhesion growth, whether forces drive changes in the size of cell-cell adhesions remains an open question. To investigate the responsiveness of adherens junctions (AJ) to force, we adapted a system of microfabricated force sensors to quantitatively report cell-cell tugging force and AJ size. We observed that AJ size was modulated by endothelial cell-cell tugging forces: AJs and tugging force grew or decayed with myosin activation or inhibition, respectively. Myosin-dependent regulation of AJs operated in concert with a Rac1, and this coordinated regulation was illustrated by showing that the effects of vascular permeability agents (S1P, thrombin) on junctional stability were reversed by changing the extent to which these agents coupled to the Rac and myosin-dependent pathways. Furthermore, direct application of mechanical tugging force, rather than myosin activity per se, was sufficient to trigger AJ growth. These findings demonstrate that the dynamic coordination of mechanical forces and cell-cell adhesive interactions likely is critical to the maintenance of multicellular integrity and highlight the need for new approaches to study tugging forces.