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J. Biol. Chem., Vol. 283, Issue 42, 28454-28463, October 17, 2008

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Biophysical Properties of Cadherin Bonds Do Not Predict Cell Sorting^*

Quanming Shi, Yuan-Hung Chien, and Deborah Leckband^¶1

From the Department of Chemical and Biomolecular Engineering, Department of Biochemistry, and ^¶Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801

Differential binding between cadherin subtypes is widely believed to mediate cell sorting during embryogenesis. However, a fundamental unanswered question is whether cell sorting is dictated by the biophysical properties of cadherin bonds, or by broader, cadherin-dependent differences in intercellular adhesion or membrane tension. This report describes atomic force microscope measurements of the strengths and dissociation rates of homophilic and heterophilic cadherin (CAD) bonds. Measurements conducted with chicken N-CAD, canine E-CAD, and Xenopus C-CAD demonstrated that all three cadherins cross-react and form multiple, intermolecular bonds. The mechanical and kinetic properties of the heterophilic bonds are similar to the homophilic interactions. The thus quantified bond parameters, together with previously reported adhesion energies were further compared with in vitro cell aggregation and sorting assays, which are thought to mimic in vivo cell sorting. Trends in quantified biophysical properties of the different cadherin bonds do not correlate with sorting outcomes. These results suggest that cell sorting in vivo and in vitro is not governed solely by biophysical differences between cadherin subtypes.

Received for publication, April 2, 2008 , and in revised form, May 21, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grant RO1 GM51338. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.

¹ To whom correspondence should be addressed: 600 South Mathews Ave., Urbana, IL 61820. Tel.: 217-244-0793; Fax: 217-333-5052; E-mail: Leckband{at}uiuc.edu.

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