The quartz crystal microbalance (QCM) was used to monitor the immobilization of tyrosinase on polycationic and polyanionic precursor assemblies in situ and in real-time. The resulting enzymatic surfaces were then exposed to various flavonoids, and the degree of binding was measured using QCM. We show that enzyme activity is retained when immobilized oil polycationic films (flavonoid binding observed), while the active site is blocked when assembled on a polyanionic film (no flavonoid binding to the enzyme). We rationalize these observations by considering a combination of interlayer interpenetration and strong electrostatic interactions between the polyelectrolyte and tyrosinase's dicopper 2(+) center. Ion-pair formation between anionic moieties of the polyanion and the metal-coordinated active site is suggested as the dominant mechanism leading to the deactivation of tyrosinase. We are currently working to expand this research to achieve a more general theory of how various metal-coordinated enzymes react with polyelectrolyte surfaces or varying structural morphology, charge density, and chemical composition.