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J Cell Sci. 2007 Nov 15;120(Pt 22):3965-76. Epub 2007 Oct 30.

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

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  • 1Department of Tumour Immunology (278), Nijmegen Centre for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Centre, PO Box 9101, 6500HB Nijmegen, The Netherlands.

Abstract

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.

PMID:
17971418
[PubMed - indexed for MEDLINE]
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