Lipid self-assembly dependence on hyaluronic acid size reveals biolubrication and osteoarthritic degeneration mechanisms

Hyaluronic acid (HA) and phospholipids (PLs) are key components of joint lubrication. In osteoarthritis (OA), the molecular weight (MW) of HA is reduced, which has been proposed to weaken the anchoring capacity of PL and impair lubrication. This study reveals a different mechanism by directly linking the MW to the structure of HA-PL (hybrid) assemblies and frictional properties. Using mixed-MW HA and PL to model this difference between healthy and OA synovial composition, we found interfacial lamellar structures form under healthy-like conditions, while hybrid vesicles predominate in OA-like conditions. At physiologically relevant shear rates, lamellar assemblies maintain ultralow friction, whereas vesicles are removed, causing a tenfold friction increase. These findings provide mechanistic insight into how HA-PL structural organization controls lubrication. While this simplified system does not capture the biochemical complexity of synovial fluid, this study advances understanding and offers a framework for designing structure-informed therapeutic strategies and biomimetic lubricants.