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

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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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