Physical crosslinking of hyaluronic acid in the presence of phospholipids in an aqueous nano-environment.

Hyaluronic acid and phospholipids are two components in the synovial joint cavity that contribute to joint lubrication synergistically. Molecular dynamics simulations were performed and hydrogen bonds in hyaluronic acid were analyzed to identify specific sites that are responsible for its physical cross-linking. Two molecular masses of hyaluronic acid, 10 kDa and 160 kDa, were considered. We use molecular dynamics simulations and the small world network approach to investigate dynamic couplings using a distance map applied to oxygen atoms in a chain of hyaluronic acid in the presence of phospholipids and water. The distance characterizing the coupling can be defined in various ways to bring out the most evident differences between various scenarios of the polymer chain conformation We show herein a physical distance understood as H-bond length and classes of these distances which are defined in a coarse-grained picture of the molecule. Simulation results indicate that addition of phospholipids has little influence on hyaluronic acid crosslinking. However, longer chains and addition of lipids promote appreciably long lasting (resilient) networks that may be of importance in biological systems. Specific sites for hydrogen bonding of phospholipids to hyaluronic acid have also been identified.