Nonadditive Interactions Mediated by Water at Chemically Heterogeneous Surfaces: Nonionic Polar Groups and Hydrophobic Interactions

We explore how two nonionic polar groups (primary amine and primary amide) influence hydrophobic interactions of neighboring nonpolar domains. We designed stable β-peptide sequences that generated globally amphiphilic (GA) helices, each with a nonpolar domain formed by six cyclohexyl side chains arranged along one side of the 14-helix. The other side of the helix was dominated by three polar side chains, from β3-homolysine (K) and/or β3-homoglutamine (Q) residues. Variations in this polar side chain array included exclusively β3-hLys (GA-KKK) and β3-hLys/β3-hGln mixtures (e.g., GA-QKK and GA-QQK). Chemical force measurements in aqueous solution versus methanol allowed quantification of the hydrophobic interactions of the β-peptide with the nonpolar tip of an atomic force microscope (AFM). At pH 10.5, where the K side chain is largely uncharged, we measured hydrophobic adhesive interactions mediated by GA-KKK to be 0.61 ± 0.04 nN, by GA-QKK to be 0.54 ± 0.01 nN, and by GA-QQK to be 0 ± 0.01 nN. This findin...