Surface plasmon resonance analysis of Alzheimer's beta-amyloid aggregation on a solid surface: From monomers to fully-grown fibrils

Abstract

We analyzed the aggregation of Alzheimer's β-amyloid (1-42) (Aβ42) peptides from fresh monomers to fully grown fibrils by using in situ surface plasmon resonance (SPR) spectrometry and ex situ atomic force microscopy (AFM). To immobilize Aβ42 peptide on an SPR chip surface, different carboxy-terminated surfaces were investigated: (1) self-assembled monolayer of 11-mercaptoundecanoic acid and (2) carboxylated dextran-modified surface. It was found that the carboxylated dextran surface was more appropriate due to a much lower degree of nonspecific binding. By using the carboxylated dextran surface, we further investigated effects of key environmental factors, such as the density of surface-bound Aβ42, the concentration of Aβ42 in solution phase, and the presence of Fe3+ ions on Aβ42 fibrillation. The increase in either the surface density of Aβ42 or its concentration in incubation solution highly accelerated the formation of amyloid fibrils on the chip surface. The presence of Fe3+ ions in the incubation solution induced significantly denser aggregates, resulting in a nearly 6-fold increase of SPR angle shift. This work shows that SPR analysis coupled with AFM can be effectively used for analyzing amyloid aggregation and deposition on a solid surface from the very beginning to fully grown fibrils.