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Modeling of Signal Transduction at Cell Surfaces. Diffusion-kinetics models are being developed for describing the interactions of soluble ligands with cell surface receptors. Ligand/receptor complexes are responsible for a wide variety of signaling phenomena in biological systems. For example, both paracrine and autocrine hormone signaling occur via hormone/receptor complex formation at cell surfaces. In addition, many examples from immune signaling involve this type of complex formation. Of particular interest to us at present is the interleukin-2 system, which involves two separate receptor sub-units interacting with the soluble IL-2 ligand. The models attempt to provide a correct kinetic analysis of the formation of receptor/ligand complexes. Both the three-dimensional diffusion of the free ligand and the two-dimensional diffusion within the cell membrane are included in the model. A novel approach taken in studies to date is to "label" the ligand which has interacted with the surface, but which is not bound to it, as "rebounding" ligand, or "localized-free" ligand. Results to date indicate that the model is capable of describing a wide variety of phenomena. Equilibrium binding immunoassay modeling. Models are developed for describing the equilibrium binding of ligands with surface receptors, including both bivalent ligand and bivalent receptor. In particular, application to the inter-cellular binding phenomenon is being studied, indicating the nature of the "zipper" mechanism involved in cell-cell adhesion through receptor interactions. Another system of interest is the "sandwich" assay, involving a bridging ligand between the receptor and a second ligand. |
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