Cadherin clusters stabilized by a combination of specific and nonspecific cis-interactions

Connor J. Thompson, Zhaoqian Su, Vinh H. Vu, Yinghao Wu, Deborah E. Leckband, Daniel K. Schwartz

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

We demonstrate a combined experimental and computational approach for the quantitative characterization of lateral interactions between membrane-associated proteins. In particular, weak, lateral (cis) interactions between E-cadherin extracellular domains tethered to supported lipid bilayers, were studied using a combination of dynamic single-molecule Förster Resonance Energy Transfer (FRET) and kinetic Monte Carlo (kMC) simulations. Cadherins are intercellular adhesion proteins that assemble into clusters at cell-cell contacts through cis-and trans-(adhesive) interactions. A detailed and quantitative understanding of cis-clustering has been hindered by a lack of experimental approaches capable of detecting and quantifying lateral interactions between proteins on membranes. Here single-molecule intermolecular FRET measurements of wild-type E-cadherin and cis-interaction mutants combined with simulations demonstrate that both nonspecific and specific cis-interactions contribute to lateral clustering on lipid bilayers. Moreover, the intermolecular binding and dissociation rate constants are quantitatively and independently determined, demonstrating an approach that is generalizable for other interacting proteins.

Original languageEnglish (US)
Article numbere59035
Pages (from-to)1-28
Number of pages28
JournaleLife
Volume9
DOIs
StatePublished - Sep 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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