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

Joost Te Riet, Aukje W Zimmerman, Alessandra Cambi, Ben Joosten, Sylvia Speller, Ruurd Torensma, Frank N van Leeuwen, Carl G Figdor, Frank de Lange

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)3965-76
Aantal pagina's12
TijdschriftJournal of cell science
Volume120
Nummer van het tijdschriftPt 22
DOI's
StatusGepubliceerd - 15 nov. 2007
Extern gepubliceerdJa

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