Evaluation of the Mechanical Properties of Zwitterionic Peptide Self-Assembled Monolayers and Their Interfacial Hydration via a Quartz Crystal Microbalance with Dissipation Monitoring

Biofouling severely limits the performance of biomedical devices, motivating the development of antifouling surface coatings inspired by natural hydration-based resistance mechanisms. Zwitterionic peptide self-assembled monolayers (SAMs) are promising candidates, yet the molecular origins of their mechanical and hydration properties remain insufficiently understood. Here, we investigate the assembly, viscoelastic properties, and interfacial hydration of zwitterionic peptide SAMs on gold substrates using quartz crystal microbalance with dissipation monitoring (QCM-D). Four peptide sequences (EK, DK, ER, and DR) were examined to elucidate the role of amino acid composition. Arginine-containing SAMs (ER and DR) exhibited a higher apparent elastic modulus and viscosity than lysine-containing counterparts (EK and DK), indicating enhanced mechanical rigidity arising from strong intermolecular interactions involving arginine side chains. Lysine-containing SAMs formed thicker and mechanically stable hydration layers, which provide a physical and energetic barrier that resists nonspecific protein and cell adhesion. The thicknesses of the interfacial hydration layer were evaluated using an ethanol−PBS displacement method. The estimated hydration thicknesses agree with AFM measurements, supporting the reliability of the QCM-D approach. These findings provide molecular-level insight for the rational design of peptide-based antifouling interfaces.