Probabilistic Modeling of Hyaluronan Synthesis and Secretion

The synthesis of hyaluronan (HA) from the surface of living cells is essential to the maintenance of tissues in living systems. 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 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 probabilistic model that allows an examination of secretion of HA by the synthase enzyme. This model provides two key insights. First, it provides a foundation for the prediction of HA molecular weight distributions that are tethered to, and released from, cell surfaces. This provides critical insight into both naturally occurring molecular weight distributions and those produced by in vitro synthesis. Second, it suggests that time-resolved analysis of the HA molecular weight distributions produced by living cells can reveal critical details of hyaluronan synthase function. In the future, such models may assist in the prediction of the physical properties of HA-rich materials and their response to changes in cell state.