An Electrochemistry and Computational Study at an Electrified Liquid–Liquid Interface for Studying Beta-Amyloid Aggregation

Silwane, Bongiwe; Wilson, Mark; Kataky, Ritu

Abstract

Amphiphilic peptides, such as Aß amyloids, can adsorb at an interface between two immiscible electrolyte solutions (ITIES). Based on previous work (vide infra), a hydrophilic/hydrophobic interface is used as a simple biomimetic system for studying drug interactions. The ITIES provides a 2D interface to study ion-transfer processes associated with aggregation, as a function of Galvani potential difference. Here, the aggregation/complexation behaviour of Aβ(1-42) is studied in the presence of Cu (II) ions, together with the effect of a multifunctional peptidomimetic inhibitor (P6). Cyclic and differential pulse voltammetry proved to be particularly sensitive to the detection of the complexation and aggregation of Aβ(1-42), enabling estimations of changes in lipophilicity upon binding to Cu (II) and P6. At a 1:1 ratio of Cu (II):Aβ(1-42), fresh samples showed a single DPV (Differential Pulse Voltammetry) peak half wave transfer potential (E1/2) at 0.40 V. Upon increasing the ratio of Cu (II) two-fold, fluctuations were observed in the DPVs, indicating aggregation. The approximate stoichiometry and binding properties of Aβ(1-42) during complexation with Cu (II) were determined by performing a differential pulse voltammetry (DPV) standard addition method, which showed two binding regimes. A pKa of 8.1 was estimated, with a Cu:Aβ1-42 ratio~1:1.7. Studies using molecular dynamics simulations of peptides at the ITIES show that Aβ(1-42) strands interact through the formation of β-sheet stabilised structures. In the absence of copper, binding/unbinding is dynamic, and interactions are relatively weak, leading to the observation of parallel and anti-parallel arrangements of β-sheet stabilised aggregates. In the presence of copper ions, strong binding occurs between a copper ion and histidine residues on two peptides. This provides a convenient geometry for inducing favourable interactions between folded β-sheet structures. Circular Dichroism spectroscopy (CD spectroscopy) was used to support the aggregation behaviour of the Aβ(1-42) peptides following the addition of Cu (II) and P6 to the aqueous phase.

Citation

Silwane, B., Wilson, M., & Kataky, R. (2023). An Electrochemistry and Computational Study at an Electrified Liquid–Liquid Interface for Studying Beta-Amyloid Aggregation. Membranes, 13(6), Article 584. https://doi.org/10.3390/membranes13060584

• Journal Article Type: Article
• Acceptance Date: May 29, 2023
• Online Publication Date: Jun 5, 2023
• Publication Date: 2023-06
• Deposit Date: Nov 7, 2023
• Publicly Available Date: Nov 7, 2023
• Journal: Membranes
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 6
• Article Number: 584
• DOI: https://doi.org/10.3390/membranes13060584
• Keywords: Filtration and Separation; Chemical Engineering (miscellaneous); Process Chemistry and Technology
• Public URL: https://durham-repository.worktribe.com/output/1900290