Ion-Mediated Adsorption of Amyloid-β Peptides at the Liquid/Liquid Interface: Insights from Electrochemistry and Molecular Dynamics Simulations

Understanding protein and peptide adsorption at interfaces is crucial for deciphering their roles in cellular processes, where they govern key biological processes, including aggregation mechanisms implicated in neurodegenerative diseases such as Alzheimer’s. In this study, we investigate the adsorption behavior of amyloid-β (Aβ) peptides and their Cu(II) complexes at the water/1,2-dichloroethane (DCE) interface by cyclic voltammetry (CV) and electrochemical impedance techniques, including alternating current (AC) voltammetry. The interface between two immiscible electrolyte solutions (ITIES) serves herein as a controlled system to study early-stage adsorption and ion transfer phenomena. We specifically examine Aβ1-16 and Aβ4-16 peptides, the N-terminal fragments involved in Cu(II) coordination, to resolve interfacial electrochemical signals and elucidate the molecular-scale mechanisms of adsorption. The electrochemical data are complemented by molecular dynamics (MD) simulations, enabling a structurally resolved understanding of peptide adsorption and Cu(II) binding at the interface. Our results highlight the impact of interfacial charge regulation, ion–ion interaction, and peptide conformational flexibility on Aβ adsorption, offering mechanistic insights with potential implications for Alzheimer’s disease pathology. By integrating electrochemical techniques with computational modeling, this study establishes a robust framework for probing and potentially modulating peptide behavior at soft interfaces.