Nanoscale dynamics of the cadherin-catenin complex bound to vinculin revealed by neutron spin echo spectroscopy.
David J E CallawayIain D NichollBright ShiGilbert ReyesBela FaragoZimei BuPublished in: Proceedings of the National Academy of Sciences of the United States of America (2024)
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.
Keyphrases
- cell adhesion
- epithelial mesenchymal transition
- cell proliferation
- molecular dynamics
- single molecule
- magnetic resonance
- cell migration
- cell therapy
- density functional theory
- squamous cell carcinoma
- magnetic resonance imaging
- atomic force microscopy
- machine learning
- dna methylation
- room temperature
- brain injury
- diffusion weighted