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First published online 30 October 2007
doi: 10.1242/jcs.004010

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.004010v1 120/22/3965    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by te Riet, J. Articles by de Lange, F. Search for Related Content PubMed PubMed Citation Articles by te Riet, J. Articles by de Lange, F.

Distinct kinetic and mechanical properties govern ALCAM-mediated interactions as shown by single-molecule force spectroscopy

Joost te Riet^1,2, Aukje W. Zimmerman¹, Alessandra Cambi¹, Ben Joosten¹, Sylvia Speller², Ruurd Torensma¹, Frank N. van Leeuwen¹, Carl G. Figdor^1,* and Frank de Lange^1,3,

¹ Department of Tumour Immunology (278), Nijmegen Centre for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Centre, PO Box 9101, 6500HB Nijmegen, The Netherlands
² Department of Scanning Probe Microscopy, Institute for Molecules and Materials (IMM), Radboud University Nijmegen, PO Box 9010, 6500GL Nijmegen, The Netherlands
³ Department of Cell Biology (283), Nijmegen Centre for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Centre, PO Box 9101, 6500HB Nijmegen, The Netherlands

^* Author for correspondence (e-mail: C.Figdor{at}ncmls.ru.nl)

Accepted 3 September 2007

The activated leukocyte cell adhesion molecule (ALCAM) mediates dynamic homotypic and heterotypic cellular interactions. Whereas homotypic ALCAM-ALCAM interactions have been implicated in the development and maintenance of tissue architecture and tumor progression, heterotypic ALCAM-CD6 interactions act to initiate and stabilize T-cell–dendritic-cell interactions affecting T-cell activation. The ability to resist the forces acting on the individual bonds during these highly dynamic cellular contacts is thought to be crucial for the (patho)physiology of ALCAM-mediated cell adhesion. Here, we used atomic force microscopy to characterize the relationship between affinity, avidity and the stability of ALCAM-mediated interactions under external loading, at the single-molecule level. Disruption of the actin cytoskeleton resulted in enhanced ALCAM binding avidity, without affecting the tensile strength of the individual bonds. Force spectroscopy revealed that the ALCAM-CD6 bond displayed a significantly higher tensile strength, a smaller reactive compliance and an up to 100-fold lower dissociation rate in the physiological force window in comparison to the homotypic interaction. These results indicate that homotypic and heterotypic ALCAM-mediated adhesion are governed by significantly distinct kinetic and mechanical properties, providing novel insight into the role of ALCAM during highly dynamic cellular interactions.

Key words: ALCAM, CD166, CD6, Cytoskeleton, Force spectroscopy, AFM

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