Bush Joshua, Cabe Jolene I, Conway Daniel, Maruthamuthu Venkat
Mechanical & Aerospace Engineering, Old Dominion University, Norfolk, VA 23529 USA.
Bioengineering, George Mason University, Fairfax, VA 22030.
bioRxiv. 2023 Aug 19:2023.07.28.550975. doi: 10.1101/2023.07.28.550975.
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细胞重排。上皮细胞-细胞接触形状的变化尤其依赖于E-钙黏蛋白的黏附动力学，而E-钙黏蛋白的黏附动力学直接受细胞产生的力和外力的影响。虽然之前已经报道了E-钙黏蛋白黏附的流动性及其黏附强度，但尚不清楚E-钙黏蛋白黏附动力学的这两个方面是如何相关的。在这里，我们使用磁珠拉曼细胞术，对包被E-钙黏蛋白的磁微珠与上皮细胞之间的E-钙黏蛋白黏附施加加速力斜坡，以确定这种关系。我们的方法能够确定单个黏附的黏附强度和力依赖性流动性，揭示了这些关键特征之间的直接相关性。由于之前有报道称，单独研究时α-连环蛋白在E-钙黏蛋白的流动性和黏附强度中均起作用，我们还对α-连环蛋白被敲除的上皮细胞进行了探究。我们发现，在没有α-连环蛋白的情况下，E-钙黏蛋白黏附不仅如预期的那样具有较低的黏附强度，而且流动性更强。我们观察到，α-连环蛋白是恢复 strained 细胞-细胞接触所必需的，并提出E-钙黏蛋白黏附的黏附强度和力依赖性流动性协同作用以调节细胞-细胞接触稳态。我们的方法引入了一种将力依赖性黏附流动性与黏附强度相关联的方法，并突出了α-连环蛋白在E-钙黏蛋白黏附动力学中的形态学作用。 （注：strained一词在原文中未明确其准确含义，此处保留英文未翻译）
