Cu(2+) affects amyloid-β (1-42) aggregation by increasing peptide-peptide binding forces.

Area of Science:

• Biochemistry
• Neuroscience
• Materials Science

Background:

• Alzheimer's disease (AD) is linked to amyloid-β (Aβ) protein misfolding and aggregation.
• Metal ion dyshomeostasis and their interaction with Aβ are implicated in AD pathogenesis.
• Previous studies indicate metal ions reduce the lag time of Aβ aggregation.

Purpose of the Study:

• To investigate the effect of copper ions (Cu2+) on the binding forces between two Aβ(1-42) peptides.
• To elucidate the single-molecule mechanism underlying copper-induced acceleration of Aβ aggregation.

Main Methods:

• Single molecule atomic force spectroscopy (smAFM) to measure peptide-peptide rupture force.
• Atomic force microscopy (AFM) to visualize Aβ aggregate formation.

Main Results:

• Copper ions significantly increased the unbinding force between two Aβ(1-42) peptides.
• Atomic force spectroscopy confirmed copper-induced changes in Aβ aggregation.
• Increased binding forces at the single-molecule level correlate with reduced aggregation lag times.

Conclusions:

• Copper ions act as a molecular bridge, enhancing the stability of initial Aβ peptide-peptide complexes.
• The observed increase in binding forces explains the accelerated aggregation kinetics of Aβ in the presence of copper.
• These findings provide a molecular basis for the role of metal ions in Alzheimer's disease.