Browsing by Subject "Lubricin"

Human joints are able to withstand millions of loading cycles with loads regularly more than 3 times an individual's body weight in large part due to the unique bearing properties of articular cartilage, a strong, slippery tissue that covers the ends of long bones. PRG4 is a boundary lubricating glycoprotein present on the cartilage surface and in the synovial fluid surrounding it. While evidence that PRG4 lubricates and preserves normal joint function is strong, little is known of its effect on cartilage surface properties, the mechanism by which it lubricates, or its postulated role of preventing wear on joints. The effect of PRG4 on cartilage friction, wear, structure, morphology, and the mechanisms by which it mediates these factors are studied here. Methods to study these parameters at the microscale using atomic force microscopy are also developed.

Cartilage of mice with the Prg4 gene (which expresses PRG4) deleted is shown to be different in a number of ways from wild type cartilage. The uppermost layer is thicker and less uniform and the surface is rougher and softer. There is also a loss of proteoglycans, structural components of cartilage, from the underlying superficial tissue, and apparent tissue damage in some cases. Wear in the presence of PRG4 in shown to be significantly lower than in its absence, a finding which may have direct implications for prevention and treatment of osteoarthritis. It appears that PRG4 needs to be present in solution, not merely on the cartilage surface to have this effect, indicating that adsorption properties are important for wear prevention.

Friction is the resistive force that arises when two contacting surfaces move relative to each other. Frictional interactions are important from both engineering and biological perspectives. In this research I focus on the fundamental understanding of friction on polymeric and biological surfaces in aqueous environments. First, I examine the frictional properties of a stimulus-responsive hydrogel, poly-N-isopropylacrylamide (pNIPAAm), to understand how different phase states affect its tribological properties. My measurements indicate that gels in a collapsed conformation at low shear rates, exhibit significantly larger friction than swollen gels. These differences arise from changes in surface roughness, adhesive interactions, and chain entanglements of the gel surfaces associated with the phase transition. Importantly, I show that the changes in friction, triggered by an external stimulus, are reversible.

Second, I examine details of the boundary lubrication mechanism involved in mediating friction and wear in diarthrodial joints. Specifically, I looked at the constituents of the synovial fluid, lubricin and hyaluronic acid (HA) and examined their interactions on model substrates, (1) to determine the effect of surface chemistry on adsorption using surface plasmon resonance (SPR), and (2) to study normal force interactions between these surfaces using colloidal probe microscopy (CPM). I found that lubricin is highly surface-active, adsorbed strongly onto hydrophobic, hydrophilic and also collagen surfaces. Overall, lubricin develops strong repulsive interactions. This behavior is in contrast to that of HA, which does not adsorb appreciably, nor does it develop significant repulsive interactions. I speculate that in mediating interactions at the cartilage surface, an important role of lubricin is one of providing a protective coating on cartilage surfaces that maintains the contacting surfaces in a sterically repulsive state.