Zwitterion-Conjugated Protein Coatings for Enhanced Antifouling in Complex Biofluids: Underlying Molecular Interaction Mechanisms

Biofouling can cause severe infections, device malfunctions, and failures in diagnostics and therapeutics. Proteins such as bovine serum albumin (BSA) have recently been used as coatings to resist biofouling because they combine surface anchoring and antifouling properties. However, their antifouling effectiveness will significantly deteriorate in complex biofluids with high salinity, limiting their practical applications. In this work, we developed a zwitterion-conjugated protein with enhanced antifouling capability by grafting zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) onto BSA protein via a click reaction. This conjugated protein can easily anchor on various substrates, both inorganic and organic, and exhibits efficient and broad-spectrum fouling resistance to metabolites, proteins, and complex biofluids. Even in the complex fetal bovine serum with higher salinity, the BSA@MPC coating can also maintain 99% fouling resistance robustly, over 6-fold superior to native BSA-coated surfaces in antifouling capability. Direct surface forces measurement reveals that such outstanding antifouling properties of conjugated protein BSA@MPC could be attributed to the stable hydration layer on its surface and the steric repulsion from the antipolyelectrolyte behavior of zwitterionic MPC polymer in the high-salinity environment. Our findings advance the development of protein-based functional materials and provide valuable insights for designing novel antifouling surfaces for marine, food, and bioengineering applications.