A Model for Hyaluronan Secretion into Biological Fluids

Hyaluronan (HA) is an essential biopolymer in joint tissues and synovial fluid, and changes in its molecular weight distribution have been linked to debilitating inflammatory joint conditions such as arthritis. Despite this, there is limited understanding of the physical mechanisms behind its secretion into biological fluids. HA is unique among biological polymers, as the polymer is synthesized at, and directly extruded through, the cell membrane. Current models for HA secretion have largely focused on a single enzyme, hyaluronan synthase, although no governing mechanism has been identified. In tissue observations point toward a more complex regulatory system involving additional enzymes, such as cell surface hyaluronidase, which is responsible for HA cleavage. This work presents a simple model for the synthesis and release of HA. The model makes predictions for the equilibrium molecular weight distributions of surface tethered and secreted HA. In addition, it describes the time-dependent growth and degradation of surface tethered HA. The model provides guidance for experimental investigation into rates of HA synthesis and release from the cell surface, and may act as a basis for understanding how the environment in the joint affects HA secretion into synovial fluid.