This application is concerned with the study of the molecular basis of skeletal joint lubrication in order to improve the design of artificial joint prostheses. These joints eventually fail mainly because of problems associated with inadequate lubrication and revision surgery is an increasingly expensive burden as the population ages. A better understating of such processes should lead to better strategies for minimizing lubrication breakdown in natural joints, as well as to strategies for improving lubrication and wear of prosthetic joint implants and other biological surfaces where prevention of adhesion is required. This proposal seeks to investigate the molecular basis of the remarkably efficient lubrication in mammalian synovial joints, by constructing surfaces partly analogous in structure to that of articular cartilage and measuring forces between them under strictly controlled conditions. Using a surface force balance apparatus, we intend to measure the normal and friction forces between layers of (i) negatively charged hyaluronic acid (HA)-aggrecan (ii) lubricin and HA-aggrecan and (iii) HA-aggrecan and phosphatidylcholine-based phospholipids (PL). Firstly, a pre-biotynilated HA will be attached to mica surface via streptavidin. Aggrecan, extracted from mammalian cartilage, will be added to the HA-coated mica to form supramolecular aggregates similar to those at the cartilage/synovium interface. Secondly, a well-characterized lubricin layers and in a later stage fluorescent or radio-labeled PL will be adsorbed onto the HA-aggrecan mica surface and the interactions studied. Our ultimate goal is to address the interactions between lubricin, PL and HA – the main players in synovial lubrication. At each stage of the project, mica-attached layers will be characterized using AFM, X-ray photoelectron spectroscopy and SFB, and their tribological properties will be examined, on a nanometer scale, in a wide range relevant to physiological conditions.
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