Bongiwe Silwane
An Electrochemistry and Computational Study at an Electrified Liquid–Liquid Interface for Studying Beta-Amyloid Aggregation
Silwane, Bongiwe; Wilson, Mark; Kataky, Ritu
Authors
Professor Mark Wilson mark.wilson@durham.ac.uk
Professor
Professor Ritu Kataky ritu.kataky@durham.ac.uk
Professor
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 |
Electronic ISSN | 2077-0375 |
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 |
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© 2023 by the authors. Licensee MDPI, Basel, Switzerland.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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