Proteomic characterization of particle-protein coronas shows differences between osteoarthritic and contralateral...

When synthetic particles are injected into a biofluid, proteins nonspecifically adsorb onto the particle surface and form a protein corona. Protein coronas are known to alter how particles function in blood; however, little is known about protein corona formation in synovial fluid or how these coronas change with osteoarthritis (OA). In this study, protein coronas were characterized on particles incubated within OA-affected or healthy rat knees.

First, to evaluate particle collection techniques, magnetic polystyrene particles were placed in bovine synovial fluid and separated using either magnetics or centrifugation. In a second experiment, 12 male and 12 female Lewis rats received a simulated medial meniscal injury. At 2, 5, or 8 weeks post-surgery, operated and contralateral limbs were injected with clean magnetic particles (n = 8 per timepoint). After a 4-h incubation, animals were euthanized and particles were magnetically recovered. In both experiments, protein coronas were characterized using an Orbitrap fusion mass spectrometer.

In the first experiment, the particle separation method affected the identified proteins, likely due to centrifugation forces causing some large proteins to spin-down with the particles. In the OA model, 300-500 proteins were identified in the particle-protein coronas with 35, 59, and 13 proteins differing between the OA-affected and contralateral limbs at 2, 5, and 8 weeks, respectively. In particular, plectin, a serine (or cysteine) proteinase inhibitor, and cathepsin B were more prominent in the particle-protein coronas of OA-affected knees.

Synthetic particles nonspecifically adsorb proteins in synovial fluid, and these binding events differ with OA severity.