title: Cu(2+) affects amyloid-β (1-42) aggregation by increasing peptide-peptide binding forces.
abstract: The link between metals, Alzheimer's disease (AD) and its implicated protein, amyloid-β (Aβ), is complex and highly studied. AD is believed to occur as a result of the misfolding and aggregation of Aβ. The dyshomeostasis of metal ions and their propensity to interact with Aβ has also been implicated in AD. In this work, we use single molecule atomic force spectroscopy to measure the rupture force required to dissociate two Aβ (1-42) peptides in the presence of copper ions, Cu(2+). In addition, we use atomic force microscopy to resolve the aggregation of Aβ formed. Previous research has shown that metal ions decrease the lag time associated with Aβ aggregation. We show that with the addition of copper ions the unbinding force increases notably. This suggests that the reduction of lag time associated with Aβ aggregation occurs on a single molecule level as a result of an increase in binding forces during the very initial interactions between two Aβ peptides. We attribute these results to copper ions acting as a bridge between the two peptide molecules, increasing the stability of the peptide-peptide complex.
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Francis
authors.initials: F
authors.lastname: Hane
authors.forename: Gary
authors.initials: G
authors.lastname: Tran
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Attwood
authors.forename: Zoya
authors.initials: Z
authors.lastname: Leonenko
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D018625:Microscopy, Atomic Force; D011485:Protein Binding; D055503:Protein Multimerization
chemical_list: D016229:Amyloid beta-Peptides; D003300:Copper
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