Equilibrium and dynamics of single-peptide binding to aluminum oxides: Emphasizing the role of local surface charge and hydrophobicity

Understanding the interactions between biomolecules and mineral surfaces is a fundamental challenge at the crossroads of colloid science, surface chemistry, and molecular biophysics. While peptides and amino acids are known to bind a variety of metal oxides, our understanding remains limited regarding how local surface characteristics influence these interactions at the nanoscale. This is particularly important for “real surfaces” which intrinsically exhibit heterogenous features that determines their behavior when interacting with biomolecules. Herein, we present a fresh perspective that focuses on probing local surface properties and dipeptide (Glu-Ala) binding on oxides grown on polycrystalline aluminum metal at the single-molecule level. First, a comprehensive surface characterization is performed to resolve the chemical composition and topography of two different native aluminum oxide surfaces. Then, by using atomic force microscopy (AFM) in force spectroscopy mode, we employ chemical force microscopy and colloidal probe techniques to quantify local surface charge and hydrophobicity, revealing noticeable differences between the two studied surfaces. Our findings demonstrate that both free enthalpies of adsorption (Δ_adsG°) and kinetic unbinding rates (k_off) are highly influenced by the surface characteristics probed locally, and suggest that the interaction of the dipeptide with the surfaces is dominated by van der Waals and hydrogen bonding. Beyond these fundamental insights regarding peptide–mineral interactions, this work provides methodological developments that are relevant for exploring molecular recognition mechanism, particularly on “real” oxide surfaces. Additionally, the implications of our findings extend to the design of peptide-functionalized materials and offer new perspectives on surface-mediated prebiotic chemistry, potentially relevant to the emergence of life on early Earth.