Lifetime measurements reveal kinetic differences between homophilic cadherin bonds

Marco V. Bayas, Andrew Leung, Evan Evans, Deborah E Leckband

Research output: Contribution to journalArticle

Abstract

Cadherins are multidomain adhesion proteins whose interactions direct cell sorting during histogenesis. They determine cell adhesion specificity, but prior studies failed to identify physical differences that could underlie cell sorting. These single molecule studies identify kinetic and strength differences between different cadherins. They further demonstrate that the modular extracellular architecture of cleavage stage C-cadherin supports a multistate binding mechanism. These multiple bonds exhibit a kinetic hierarchy of strengths that map to the different cadherin domains. The outer two N-terminal domains of C-cadherin form two bound states with dissociation rates of 3.9 and 0.02 s-1. The latter is 25-fold slower than between the corresponding epithelial cadherin segments. In addition to the two fast bonds, the five-domain fragment (CEC1-5) forms two additional stronger, longer-lived bonds with dissociation rates of 0.00039 and 0.00001 s-1. We further quantified the lifetimes of bonds subject to a constant force, and thus identified multiple dissociation events with rates that agree quantitatively with the force spectroscopy data. The qualitative features are similar to those reported for epithelial cadherin. However, the significant differences in the dissociation rates of the outer domains, which include the specificity-determining region, suggest that kinetic differences may determine cadherin discrimination, rather than adhesion energies.

Original languageEnglish (US)
Pages (from-to)1385-1395
Number of pages11
JournalBiophysical journal
Volume90
Issue number4
DOIs
StatePublished - Feb 2006

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Cadherins
Cell Adhesion
Cell Communication
Spectrum Analysis

ASJC Scopus subject areas

  • Biophysics

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Lifetime measurements reveal kinetic differences between homophilic cadherin bonds. / Bayas, Marco V.; Leung, Andrew; Evans, Evan; Leckband, Deborah E.

In: Biophysical journal, Vol. 90, No. 4, 02.2006, p. 1385-1395.

Research output: Contribution to journalArticle

Bayas, Marco V. ; Leung, Andrew ; Evans, Evan ; Leckband, Deborah E. / Lifetime measurements reveal kinetic differences between homophilic cadherin bonds. In: Biophysical journal. 2006 ; Vol. 90, No. 4. pp. 1385-1395.
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