In osteoarthritis the integrity of articular cartilage is damaged, compromising both the mechanical functioning and the self-repair capability of the tissue. The goal of this project is to elucidate the roles of collagen and proteoglycan in the biomechanical and homeostatic functions of normal and osteoarthritic cartilage. The specific aims of this proposal are: to characterize the molecular packing of the collagen fibrils and the fixed charged density of proteoglycans in the articular cartilage of the knee as a function of topography and age, with the view of evaluating how the structures and properties of the macromolecules in articular cartilage depend on their mechanochemical history; to characterize the mechanisms of interaction between proteoglycans and collagen as a function of age and site in articular cartilages; and to elucidate the determinants of fibril swelling and compressibility of the collagen in articular cartilage as compared to those bone and soft tissues. The fibril orientation, and their relative alignment and compressibility throughout cartilages will be determined by X-ray diffraction techniques. The axial periodicity, the lateral distances between molecules in the fibrils, and other regularities in the molecular packing will also be characterized by x-ray diffraction. The space occupied by collagen fibrils as well as the state of the charged residues in the cartilage collagen fibrils will be measured by physical chemical methods. The charge density distribution and the mechanism of action of the endogenous force fields that are generated in cartilages by proteoglycans will be characterized using optical and physical chemical methods.