Department of Chemistry and Biochemistry, City College of New York, City University of New York, New York, NY 10031.
Department of Biomedical Science and Physiology, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, United Kingdom.
Proc Natl Acad Sci U S A. 2024 Sep 24;121(39):e2408459121. doi: 10.1073/pnas.2408459121. Epub 2024 Sep 19.
We report a neutron spin echo (NSE) study of the nanoscale dynamics of the cell-cell adhesion cadherin-catenin complex bound to vinculin. Our measurements and theoretical physics analyses of the NSE data reveal that the dynamics of full-length α-catenin, β-catenin, and vinculin residing in the cadherin-catenin-vinculin complex become activated, involving nanoscale motions in this complex. The cadherin-catenin complex is the central component of the cell-cell adherens junction (AJ) and is fundamental to embryogenesis, tissue wound healing, neuronal plasticity, cancer metastasis, and cardiovascular health and disease. A highly dynamic cadherin-catenin-vinculin complex provides the molecular dynamics basis for the flexibility and elasticity that are necessary for the AJs to function as force transducers. Our theoretical physics analysis provides a way to elucidate these driving nanoscale motions within the complex without requiring large-scale numerical simulations, providing insights not accessible by other techniques. We propose a three-way "motorman" entropic spring model for the dynamic cadherin-catenin-vinculin complex, which allows the complex to function as a flexible and elastic force transducer.
我们报告了一个中子自旋回波(NSE)研究,研究了与 vinculin 结合的细胞间黏附钙黏蛋白-连环蛋白复合物的纳米级动力学。我们对 NSE 数据的测量和理论物理分析表明,全长α-连环蛋白、β-连环蛋白和 vinculin 驻留在钙黏蛋白-连环蛋白-vinculin 复合物中的动力学被激活,涉及该复合物中的纳米级运动。钙黏蛋白-连环蛋白复合物是细胞间黏附连接(AJ)的核心组成部分,对于胚胎发生、组织伤口愈合、神经元可塑性、癌症转移以及心血管健康和疾病至关重要。一个高度动态的钙黏蛋白-连环蛋白-vinculin 复合物为 AJ 作为力传感器所需的灵活性和弹性提供了分子动力学基础。我们的理论物理分析为阐明复合物内的这些驱动纳米级运动提供了一种方法,而无需进行大规模数值模拟,从而提供了其他技术无法获得的见解。我们提出了一个三向“动力传递者”熵弹簧模型,用于动态钙黏蛋白-连环蛋白-vinculin 复合物,使复合物能够作为灵活和弹性的力传感器发挥作用。