Predicting Pericellular Matrix Structure from Simple Models of Hyaluronan Secretion

The synthesis and release of hyaluronan (HA) from the surface of living cells is essential to the maintenance of living tissues and fluids. HA synthesis is controlled by the hyaluronan synthase enzyme, which assembles the polymer chain, and extrudes it through the cell membrane before it is released into the extracellular space. This enzymatic process forms a critical link between the state of the cellular system (protein expression, metabolism, etc) and the properties of cellular interfaces, the extracellular matrix and many biofluids. I present a simple kinetic model that allows an examination of the secretion process. This model enables simulation of the synthesis and release process, enabling prediction of the molecular weight distributions of HA that are tethered to, and released from the cell surface. In so doing this model offers direct insight into the structure of the pericellular matrix, a cell tethered, hyaluronan-rich interface that mediates many cell processes such as adhesion and cell surface access. In addition, the simulations suggest that time-resolved analysis of the hyaluronan molecular weight distributions produced by living cells after PCM digestion can reveal critical details of hyaluronan synthase function.