Biological specificity and measurable physical properties of cell surface receptors and their possible role in signal transduction through the cytoskeleton

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.