Kinetic analysis of beta-amyloid peptide aggregation induced by metal ions based on surface plasmon resonance biosensing.
Recent studies suggest that beta-amyloid (Abeta) aggregation and toxicity are facilitated by metal ions. This study aims to evaluate the kinetics of Abeta aggregation/dissociation in the presence of metal ions and to investigate the efficacy of a metal chelator to disrupt the metal ion-induced Abeta aggregates. Soluble Abeta(1-40) peptide was immobilized on a surface plasmon resonance biosensing surface and aggregation induced by contact with soluble Abeta with or without metal ions. Our study revealed that all the tested metal ions promoted Abeta 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 Abeta aggregates were unstable. Other ions attained the maximum Abeta binding at much longer times: 45 min for Ca(II), 60 min for Fe(II), Fe(III), and Zn(II) ions. The Abeta aggregates induced by Fe(III) ions had the greatest stability. The metal ion-induced Abeta(1-40) aggregates could be disrupted by the metal chelator, EDTA, suggesting a metal chelator may serve as a pharmacological agent to interfere with Abeta aggregation. Finally, this study demonstrates that the SPR biosensor can be an effective and efficient setup to investigate the mechanism of Abeta aggregation.
Hu
Wen-Pin
WP
Institute of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
Chang
Guan-Liang
GL
Chen
Shean-Jen
SJ
Kuo
Yu-Min
YM
D000465:Algorithms; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000276:immunology; D000906:Antibodies / Q000737:chemistry; D000937:Antigen-Antibody Reactions; D015374:Biosensing Techniques; D002021:Buffers; D002614:Chelating Agents; D004492:Edetic Acid; D007700:Kinetics; D008670:Metals / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry; D012965:Sodium Chloride; D020349:Surface Plasmon Resonance; D013499:Surface Properties
D016229:Amyloid beta-Peptides; D000906:Antibodies; D002021:Buffers; D002614:Chelating Agents; D008670:Metals; D010710:Phosphates; D012965:Sodium Chloride; D004492:Edetic Acid