O-glycans Expand Lubricin and Attenuate its Viscosity and Shear Thinning

Lubricin, an intrinsically disordered glycoprotein, plays a pivotal role in facilitating smooth movement and ensuring the enduring functionality of synovial joints. The central domain of this protein serves as a source of this excellent lubrication, and is characterized by its highly glycosylated, negatively charged, and disordered structure. However, the influence of O-glycans on the viscosity of lubricin remains unclear. In this study, we employ molecular dynamics simulations in absence and presence of shear, along with continuum simulations, to elucidate the intricate interplay between O-glycans and lubricin and the impact of O-glycans on lubricins conformational properties and viscosity. We find the presence of O-glycans to induce a more extended conformation in fragments of the disordered region of lubricin. These O-glycans contribute to a reduction in solution viscosity but at the same time weaken shear thinning at high shear rates, compared to non-glycosylated systems with the same density. This effect is attributed to the steric and electrostatic repulsion between the fragments, which prevent their conglomeration and structuring. Our computational study yields a mechanistic mechanism underlying previous experimental observations of lubricin and paves the way to more rationally understanding its function in the synovial fluid.