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Facet-Dependent Interactions of Islet Amyloid Polypeptide with Gold Nanoparticles: Implications for Fibril Formation and Peptide-Induced Lipid Membrane Disruption

Wang, Shih-Ting, Lin, Yiyang, Todorova, Nevena, Xu, Yingqi, Mazo, Manuel, Rana, Subinoy, Leonardo, Vincent, Amdursky, Nadav, Spicer, Christopher D., Alexander, Bruce D., and others. (2017) Facet-Dependent Interactions of Islet Amyloid Polypeptide with Gold Nanoparticles: Implications for Fibril Formation and Peptide-Induced Lipid Membrane Disruption. Chemistry of Materials, 29 (4). pp. 1550-1560. ISSN 0897-4756. E-ISSN 1520-5002. (doi:10.1021/acs.chemmater.6b04144) (KAR id:61374)

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http://dx.doi.org/10.1021/acs.chemmater.6b04144

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 (a helix and beta-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.

Item Type: Article
DOI/Identification number: 10.1021/acs.chemmater.6b04144
Uncontrolled keywords: Medway School of Pharmacy
Subjects: Q Science
Q Science > QD Chemistry
Q Science > QD Chemistry > QD473 Physical properties in relation to structure
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Alison Edwards
Date Deposited: 18 Apr 2017 14:42 UTC
Last Modified: 12 Feb 2020 04:09 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/61374 (The current URI for this page, for reference purposes)
Edwards, Alison A.: https://orcid.org/0000-0002-4637-9373
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