The goals of the proposed work are essentially twofold: First, to determine experimentally the physical properties of glycosaminoglycans (chiefly hyaluronate, heparin and chondroitin sulfate) and their higher structures (proteoglycan subunits and aggregates), and to relate these critically to contemporary polyelectrolyte theories, in order to verify, modify and improve such theoretical understanding. Laser light scattering, fluorescence recovery after photobleaching (FRAP) and HPLC are the chief experimental techniques to be used. Monte Carlo simulations will also be used as an adjunct for interpreting experimental results and modeling polyelectrolyte thermodynamics and static properties. Second, the properties of the glycosaminoglycans determined experimentally and interpreted within the framework of the best existing physical theories are to be related to their diverse physiological functions, including the compressibility and swelling pressure of connective tissues, the control of solute flow, and glycosaminoglycan interactions with protein in such tissues. These results, together with proposed experiments to study degradation processes of glycosaminoglycans, may also aid in understanding the basis of such connective tissue diseases as arthritis.
