title: Facet-Dependent Interactions of Islet Amyloid Polypeptide with Gold Nanoparticles: Implications for Fibril Formation and Peptide-Induced Lipid Membrane Disruption.
abstract: A comprehensive understanding of the mechanisms of interaction between proteins or peptides and nanomaterials is crucial for the development of nanomaterial-based diagnostics and therapeutics. In this work, we systematically explored the interactions between citrate-capped gold nanoparticles (AuNPs) and islet amyloid polypeptide (IAPP), a 37-amino acid peptide hormone co-secreted with insulin from the pancreatic islet. We utilized diffusion-ordered spectroscopy, isothermal titration calorimetry, localized surface plasmon resonance spectroscopy, gel electrophoresis, atomic force microscopy, transmission electron microscopy (TEM), and molecular dynamics (MD) simulations to systematically elucidate the underlying mechanism of the IAPP-AuNP interactions. Because of the presence of a metal-binding sequence motif in the hydrophilic peptide domain, IAPP strongly interacts with the Au surface in both the monomeric and fibrillar states. Circular dichroism showed that AuNPs triggered the IAPP conformational transition from random coil to ordered structures (α-helix and β-sheet), and TEM imaging suggested the acceleration of IAPP fibrillation in the presence of AuNPs. MD simulations revealed that the IAPP-AuNP interactions were initiated by the N-terminal domain (IAPP residues 1-19), which subsequently induced a facet-dependent conformational change in IAPP. On a Au(111) surface, IAPP was unfolded and adsorbed directly onto the Au surface, while for the Au(100) surface, it interacted predominantly with the citrate adlayer and retained some helical conformation. The observed affinity of AuNPs for IAPP was further applied to reduce the level of peptide-induced lipid membrane disruption.
authors.affiliation: Department of Materials, Imperial College London, London SW7 2AZ, U.K.; Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, U.K.
authors.forename: Shih-Ting
authors.initials: ST
authors.lastname: Wang
authors.affiliation: Department of Materials, Imperial College London, London SW7 2AZ, U.K.; Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, U.K.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Lin
authors.affiliation: School of Engineering, RMIT University , GPO Box 2476, Melbourne, Victoria 3001, Australia.
authors.forename: Nevena
authors.initials: N
authors.lastname: Todorova
authors.affiliation: Department of Life Sciences, Imperial College London , London SW7 2AZ, U.K.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Materials, Imperial College London, London SW7 2AZ, U.K.; Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, U.K.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mazo
authors.affiliation: Department of Materials, Imperial College London, London SW7 2AZ, U.K.; Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, U.K.
authors.forename: Subinoy
authors.initials: S
authors.lastname: Rana
authors.affiliation: Department of Materials, Imperial College London, London SW7 2AZ, U.K.; Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, U.K.
authors.forename: Vincent
authors.initials: V
authors.lastname: Leonardo
authors.affiliation: Department of Materials, Imperial College London, London SW7 2AZ, U.K.; Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, U.K.
authors.forename: Nadav
authors.initials: N
authors.lastname: Amdursky
authors.affiliation: Department of Materials, Imperial College London, London SW7 2AZ, U.K.; Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, U.K.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Spicer
authors.affiliation: Department of Pharmaceutical, Chemical and Environmental Science, University of Greenwich , Central Avenue, Chatham, Kent ME4 4TB, U.K.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Alexander
authors.affiliation: Medway School of Pharmacy, Universities of Kent and Greenwich at Medway , Central Avenue, Chatham, Kent ME4 4TB, U.K.
authors.forename: Alison A
authors.initials: AA
authors.lastname: Edwards
authors.affiliation: Department of Life Sciences, Imperial College London , London SW7 2AZ, U.K.
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Matthews
authors.affiliation: School of Engineering, RMIT University , GPO Box 2476, Melbourne, Victoria 3001, Australia.
authors.forename: Irene
authors.initials: I
authors.lastname: Yarovsky
authors.affiliation: Department of Materials, Imperial College London, London SW7 2AZ, U.K.; Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, U.K.
authors.forename: Molly M
authors.initials: MM
authors.lastname: Stevens