Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana, IL 61801, USA.
J Cell Sci. 2012 Sep 15;125(Pt 18):4362-71. doi: 10.1242/jcs.105775. Epub 2012 Jun 20.
This study investigates the relationship between classical cadherin binding affinities and mechanotransduction through cadherin-mediated adhesions. The mechanical properties of cadherin-dependent intercellular junctions are generally attributed to differences in the binding affinities of classical cadherin subtypes that contribute to cohesive energies between cells. However, cell mechanics and mechanotransduction may also regulate intercellular contacts. We used micropipette measurements to quantify the two-dimensional affinities of cadherins at the cell surface, and two complementary mechanical measurements to assess ligand-dependent mechanotransduction through cadherin adhesions. At the cell surface, the classical cadherins investigated in this study form both homophilic and heterophilic bonds with two-dimensional affinities that differ by less than threefold. In contrast, mechanotransduction through cadherin adhesions is strongly ligand dependent such that homophilic, but not heterophilic ligation mediates mechanotransduction, independent of the cadherin binding affinity. These findings suggest that ligand-selective mechanotransduction may supersede differences in cadherin binding affinities in regulating intercellular contacts.
本研究探讨了经典钙黏蛋白结合亲和力与钙黏蛋白介导线粒体黏附介导的机械转导之间的关系。钙黏蛋白依赖性细胞间连接的力学性质通常归因于经典钙黏蛋白亚型结合亲和力的差异，这些差异导致了细胞间的内聚能。然而，细胞力学和机械转导也可能调节细胞间接触。我们使用微管测量法来量化细胞表面钙黏蛋白的二维亲和力，并使用两种互补的力学测量方法来评估通过钙黏蛋白黏附介导的配体依赖性机械转导。在细胞表面，本研究中研究的经典钙黏蛋白与二维亲和力相差不到三倍的同型和异型结合形成键。相比之下，通过钙黏蛋白黏附的机械转导强烈依赖于配体，即同型但非异型连接介导机械转导，而与钙黏蛋白结合亲和力无关。这些发现表明，配体选择性机械转导可能取代钙黏蛋白结合亲和力的差异，从而调节细胞间接触。
