Rheological effects of macromolecular interactions in synovial fluid.

The rheological properties of synovial fluid (SF) are largely attributed to the presence of high molecular weight hyaluronan (HA). However, rheological differences between SF and pure HA solutions suggest that SF proteins actively contribute towards the bulk viscoelasticity of this biological fluid. Due to various experimental challenges involved with the rheometry of low-viscosity biological fluids, the macromolecular interactions in SF and their relative rheological importance are still a matter of active discussion. Interestingly however, recent evidence suggests that the concentration and structure of proteoglycan 4 (PRG4, also known as lubricin) can directly modulate the viscoelastic properties of HA-PRG4 solutions. The objective of this review is to highlight recent rheological studies that examine the macromolecular interactions between HA and proteins in SF. First, a general overview of the chemical composition of SF and the molecular structure of its key constituents HA and PRG4 is provided. Subsequently, diverse rheological experimental techniques that have been developed to characterize HA solutions are discussed. Finally, rheological investigations of macromolecular interactions between HA, serum proteins, and PRG4 are examined. This review illustrates how diverse rheological techniques can expand our understanding of the composition-structure-function relationships in SF.