It is widely recognized that PCs form around charged NPs in protein-rich environments, yet studies investigating the consequences of more specific individual ECM components on NP interactions have not been elucidated. By utilizing highly active enzymes found in OA, our goal was to determine whether the enzymatically released biomolecules interact with the NPs. Atomic force microscopy (AFM) was employed to analyze macroscopic structures in the supernatants from ex vivo cartilage explants preconditioned with specific catabolic enzymes pertinent to OA and subsequently incubated with cationic NPs. Distinct aggregate morphologies were detected for each condition as shown in Figure .