Hydration and antibiofouling of TMAO-derived zwitterionic polymers surfaces studied with atomistic molecular dynamics simulations

Zwitterionic polymers have emerged as a class of highly effective ultralow fouling materials for critical marine coating and biomedical applications. The recently developed trimethylamine N-oxide (TMAO)-derived zwitter-ionic polymers have demonstrated excellent antibiofouling capability in various chemical environments; how-ever, it remains unclear how they interact with proteins at the microscopic level. To further investigate the antifouling mechanisms, we performed atomistic molecular dynamics (MD) simulations in combination with free-energy computations to provide an in-depth molecular understanding of the interactions of TMAO polymer brush (pTMAO) surfaces with proteins of opposite charges (positively charged lysozyme and negatively charged barnacle cement protein) in aqueous environments (pure water and saline solution). Our simulations revealed ordered structures of a condensed hydration water layer on the pTMAO surfaces in pure and saline water. The quantitative free energy analyses showed that the pTMAO surface has small protein desorption energy, but with a strong hydration energy barrier near the polymer surfaces to resist protein adsorption compared to other biofouling surfaces. The addition of salts only has a slight effect on the pTMAO surface's exclusion of proteins due to the small interference of the structure of interfacial water. This study provides detailed knowledge of the strong surface hydration of zwitterionic polymers and its relation to salt impact, protein adsorption, and anti-biofouling behavior of these important materials.