Hari O. S. Yadav, An-Tsung Kuo, Shingo Urata, Kosuke Funahashi, Yutaka Imamura and Wataru Shinoda*
Phys Chem Chem Phys, 24, 14805-14815 (2022).
Self-assembled monolayers (SAMs) and polymers are used for the surface modification of biomedical implants in biomedical applications. To improve the biocompatibility of SAMs and polymers and evoke appropriate host responses, a precise understanding of their interactions with biological materials is required. In this study, molecular dynamics simulations were conducted to investigate the adsorption behavior of a variety of amino acid side chain analogs (SCAs) and a peptide, β-hairpin (HP7), which was selected as a minimum model of proteins, on a series of liquid-like SAMs with terminal functional groups of –OH, –OCH3, –CH3, and –CF3 and chain length ranging between 5 – 6 atoms. The relationship between the adsorption free energy and the type of SCA as well as the interfacial properties of water on the SAMs were examined to determine the acute predictors of protein adsorption properties on the SAM surfaces. We also investigated the structural change of HP7 on the SAM surfaces to understand the relationship between the surface interactions and denaturation. The adsorption free energy was found to be linearly related to the surface hydrophobicity, which was computed as the free energy of cavity formation near the SAM–water interfaces. The results showed that the hydrophobic surfaces with –CH3 and –CF3 terminals evoked substantial conformational changes in HP7 owing to the strong hydrophobic attractions to TRP residues of HP7. Similarly, the hydrophilic surface terminated by –OH also promoted the structural change of HP7 owing to the strong hydrogen bonds between the hydrophilic tail and ASN, GLU, LYS, PRO, and THR residues of HP7. Consequently, the moderate amphiphilic surface terminated by –OCH3 avoided denaturation of HP7 the most efficiently, thus improving the biocompatibility of the surface. In conclusion, our results provided a deep understanding of a protein adsorption for a wide range of polymeric surfaces, which can potentially aid the design of appropriate biocompatible coatings for medical applications.