Kinetic analysis of β-amyloid peptide aggregation induced by metal ions based on surface plasmon resonance biosensing

Recent studies suggest that β-amyloid (Aβ) aggregation and toxicity are facilitated by metal ions. This study aims to evaluate the kinetics of Aβ aggregation/dissociation in the presence of metal ions and to investigate the efficacy of a metal chelator to disrupt the metal ion-induced Aβ aggregates. Soluble Aβ(1–40) peptide was immobilized on a surface plasmon resonance biosensing surface and aggregation induced by contact with soluble Aβ with or without metal ions. Our study revealed that all the tested metal ions promoted Aβ aggregation but with different kinetics. Among them, Cu(II) ions had the highest association constant, and reached the maximum binding in 10 min. However, the Cu(II)-induced Aβ aggregates were unstable. Other ions attained the maximum Aβ binding at much longer times: 45 min for Ca(II), 60 min for Fe(II), Fe(III), and Zn(II) ions. The Aβ aggregates induced by Fe(III) ions had the greatest stability. The metal ion-induced Aβ(1–40) aggregates could be disrupted by the metal chelator, EDTA, suggesting a metal chelator may serve as a pharmacological agent to interfere with Aβ aggregation. Finally, this study demonstrates that the SPR biosensor can be an effective and efficient setup to investigate the mechanism of Aβ aggregation.