Cu2+ Affects Amyloid-\b{eta} (1-42) Aggregation by Increasing Peptide-Peptide Binding Forces

Abstract

The link between metals, Alzheimers disease (AD) and its implicated protein, amyloid \b{eta} (A\b{eta}), is complex and highly studied. AD is believed to occur as a result of the misfolding and aggregation of A\b{eta}. The dyshomeostasis of metal ions and their propensity to interact with A\b{eta} 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 A\b{eta} (1 42) peptides in the presence of copper ions, Cu2+. In addition, we use atomic force microscopy to resolve the aggregation of A\b{eta} formed. Previous research has shown that metal ions decrease the lag time associated with A\b{eta} 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 A\b{eta} aggregation occurs on a single molecule level as a result of an increase in binding forces during the very initial interactions between two A\b{eta} 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.