Elastic versus brittle mechanical responses predicted for dimeric cadherin complexes

Neel, Brandon L.; Nisler, Collin; Walujkar, Sanket; Araya-Secchi, Raúl; Sotomayor, Marcos

doi:10.1016/j.bpj.2022.02.007

Cited by 4 publications

(1 citation statement)

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“…However, limited attention has been given to variations in the EC5-EC5 distance during adhesion. Crystal lattice studies have identified EC5-EC5 distances of 29 nm for the X-dimer, 37 nm for the S-dimer, and 19 nm for the cis-cluster of E-cad (20, 29, 30). These changes in EC5-EC5 distance offer an alternative means of monitoring E-cad adhesion; however, resolving such minute distance changes requires a high-resolution technique.…”

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confidence: 99%

Observation of E-cadherin Adherens Junction Dynamics with Metal-Induced Energy Transfer Imaging and Spectroscopy

Chen,

Karedla,

Enderlein

2023

Preprint

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Epithelial cadherin (E-cad) mediated cell-cell junctions play a crucial role in the establishment and maintenance of tissues and organs. In this study, we employed metal-induced energy transfer imaging and spectroscopy to investigate variations in intermembrane distance during adhesion between two model membranes adorned with E-cad. By correlating the measured intermembrane distances with the distinct E-cad junction states, as determined by their crystal structures, we probed the dynamic behavior and diversity of E-cad junctions across different binding pathways.Our observations led to the identification of a transient intermediate state referred to as the X-dimeric state and enabled a detailed analysis of its kinetics. We discovered that the formation of the X-dimer leads to significant membrane displacement, subsequently impacting the formation of other X-dimers. These direct experimental insights into the subtle dynamics of E-cad-modified membranes and the resultant changes in intermembrane distance provide novel perspectives on the assembly of E-cad junctions between cells. This knowledge en-hances our comprehension of tissue and organ development and may serve as a foundation for the development of innovative therapeutic strategies for diseases linked to cell-cell adhesion abnormalities.Significance StatementIn this study, we employed metal-induced energy transfer (MIET) imaging and spectroscopy to track variations in intermembrane distance during the adhesion of two membranes mediated by epithelial cadherin. Leveraging the high spatial resolution of MIET, we explored the dynamics of cadherins across various binding pathways. Furthermore, we successfully captured a transient intermediate state known as the X-dimer and revealed its ability to communicate with other X-dimers through membrane displacement. These discoveries offer valuable mechanistic insights into the dynamics of cadherin junctions.

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confidence: 99%