Liu Zhijun, Tan John L, Cohen Daniel M, Yang Michael T, Sniadecki Nathan J, Ruiz Sami Alom, Nelson Celeste M, Chen Christopher S
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):9944-9. doi: 10.1073/pnas.0914547107. Epub 2010 May 12.
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.
肌动球蛋白收缩性部分通过在细胞-基质和细胞-细胞接触位点产生机械力来影响组织内的细胞组织。虽然细胞-基质黏附处机械负荷增加会导致黏着斑生长，但力是否驱动细胞-细胞黏附大小的变化仍是一个悬而未决的问题。为了研究黏附连接（AJ）对力的反应性，我们采用了一种微制造力传感器系统来定量报告细胞-细胞拉力和AJ大小。我们观察到AJ大小受内皮细胞-细胞拉力调节：AJ和拉力分别随肌球蛋白激活或抑制而增大或减小。肌球蛋白对AJ的依赖性调节与Rac1协同作用，血管通透性剂（S1P、凝血酶）对连接稳定性的影响可通过改变这些试剂与Rac和肌球蛋白依赖性途径的偶联程度而逆转，这说明了这种协同调节。此外，直接施加机械拉力而非肌球蛋白活性本身就足以触发AJ生长。这些发现表明，机械力与细胞-细胞黏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，并突出了研究拉力的新方法的必要性。
