Mechanical & Aerospace Engineering, Old Dominion University, Norfolk, VA, 23529, USA; Bioengineering, George Mason University, Fairfax, VA, 22030, USA.
Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Biochem Biophys Res Commun. 2023 Nov 19;682:308-315. doi: 10.1016/j.bbrc.2023.09.077. Epub 2023 Oct 4.
Tissue remodeling and shape changes often rely on force-induced cell rearrangements occurring via cell-cell contact dynamics. Epithelial cell-cell contact shape changes are particularly dependent upon E-cadherin adhesion dynamics which are directly influenced by cell-generated and external forces. While both the mobility of E-cadherin adhesions and their adhesion strength have been reported before, it is not clear how these two aspects of E-cadherin adhesion dynamics are related. Here, using magnetic pulling cytometry, we applied an accelerated force ramp on the E-cadherin adhesion between an E-cadherin-coated magnetic microbead and an epithelial cell to ascertain this relationship. Our approach enables the determination of the adhesion strength and force-dependent mobility of individual adhesions, which revealed a direct correlation between these key characteristics. Since α-catenin has previously been reported to play a role in both E-cadherin mobility and adhesion strength when studied independently, we also probed epithelial cells in which α-catenin has been knocked out. We found that, in the absence of α-catenin, E-cadherin adhesions not only had lower adhesion strength, as expected, but were also more mobile. We observed that α-catenin was required for the recovery of strained cell-cell contacts and propose that the adhesion strength and force-dependent mobility of E-cadherin adhesions act in tandem to regulate cell-cell contact homeostasis. Our approach introduces a method which relates the force-dependent adhesion mobility to adhesion strength and highlights the morphological role played by α-catenin in E-cadherin adhesion dynamics.
组织重塑和形状变化通常依赖于通过细胞-细胞接触动力学发生的力诱导的细胞重排。上皮细胞-细胞接触形状变化特别依赖于 E-钙黏蛋白粘附动力学，其直接受细胞产生的和外部力的影响。虽然 E-钙黏蛋白黏附的流动性及其黏附强度以前已经有报道，但尚不清楚 E-钙黏蛋白黏附动力学的这两个方面如何相关。在这里，我们使用磁拉细胞术，在 E-钙黏蛋白涂覆的磁性微球和上皮细胞之间的 E-钙黏蛋白粘附上施加加速力斜坡，以确定这种关系。我们的方法能够确定单个粘附的粘附强度和力依赖性的流动性，这揭示了这两个关键特征之间的直接相关性。由于α-连环蛋白以前在独立研究时已被报道在 E-钙黏蛋白的流动性和粘附强度中都发挥作用，因此我们还探测了α-连环蛋白已被敲除的上皮细胞。我们发现，在缺乏α-连环蛋白的情况下，E-钙黏蛋白粘附不仅如预期的那样具有较低的粘附强度，而且还具有更高的流动性。我们观察到α-连环蛋白是恢复应变细胞-细胞接触所必需的，并提出 E-钙黏蛋白粘附的粘附强度和力依赖性流动性协同作用以调节细胞-细胞接触的动态平衡。我们的方法引入了一种将力依赖性粘附流动性与粘附强度相关联的方法，并突出了α-连环蛋白在 E-钙黏蛋白粘附动力学中的形态作用。
