Biological specificity and measurable physical properties of cell surface receptors and their possible role in signal transduction through the cytoskeleton G. Forgacs Abstract: It is proposed that the binding specificities of cell adhesion molecules are manifested in their measurable physical properties. A method specifically designed to measure the interfacial tension of cell aggregates is described. With the introduction of a statistical mechanical model, the measured values of tensions for aggregates consisting of genetically engineered cells with controlled adhesive properties are used to obtain information on the strength of individual receptor-ligand bonds. The strength of binding must depend on the receptor and its ligand and reflects the amino acid sequence of the binding proteins. Many of the cell surface receptors, being transmembrane proteins, are attached to the various macromolecular networks of the cytoskeleton; therefore, it is suggested that their ligation and ensuing conformational change may substantially affect the mechanical state of the cytoskeletal assemblies. Since these assemblies are believed to actively participate in intracellular signaling by transmitting signals from the cell membrane into the nucleus, the cell adhesion molecules may influence signaling in a predictable way through their measurable physical characteristics. In particular, varying bond strength at the cell surface may lead to differential gene regulation. Key words: cell adhesion, surface tension, signaling, network, filament. R6sm6 : I1 est propost que la sptcificitt de liaison des molkcules d'adhtrence cellulaire est dktenninbes par leurs propriktts physiques mesurables. Nous dtcrivons une mbthode mise au point spkcifiquement pour mesurer la tension P l'interface d'agrkgats cellulaires. Grsce P un modkle mkcanique statistique, les valeurs des tensions mesurkes dans des agrkgats de cellules modifites par gknie gknttique et ayant des propriktks spkcifiques d'adhbrence sont utilistes pour dtterminer la force de liaison entre un rkepteur et un ligand. La force de liaison dkpend nkcessairement du rkcepteur et de son ligand et elle dkcoule de la sequence d'acides arnints des prottines d'adhtrence. En considkrant que plusieurs r6cepteurs membranaires cellulaires sont des prottines transmembranaires et sont ainsi reliks P divers rkseaux macromolkulaires du cytosquelette, nous suggkrons que les changements de configuration constcutifs h la fixation d'un ligand au rkcepteur pourraient modifier substantiellement les proprittks mtcaniques des divers assemblages du cytosquelette. Puisque ces assemblages participeraient activement au mtcanisme de signalisation intracellulaire en transmettant des signaux de la membrane cellulaire jusqu'h l'inttrieur du noyau, les moltcules d'adhbrence cellulaire influenceraient la signalisation d'une f a ~ o n prkvisible grdce P leurs propriktks physiques mesurables. En particulier, la variation de la force de liaison h la surface cellulaire pourrait entrainer une rkgulation genique difftrentielle. Mots clis : adhtsion cellulaire, tension superficielle, rkseau de signalisation, filament. [Traduit par la redaction] Received April 7, 1995. Accepted July 17, 1945. Abbreviations: ECM, extracellular matrix; CAM, cell adhesion molecule; SAM, substrate adhesion molecule. G. Forgacs. Department of Physics and Biology, Clarkson University, Potsdarn, NY 13699-5820, U.S.A. Biochern. Cell Biol. 73: 317-326 (1995). Printed in Canada 1 Imprim6 au Canada Biochem. Cell Biol. Downloaded from www.nrcresearchpress.com by Hubei university on 06/04/13 For personal use only.