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 beta-amyloid (1-42) (A beta 42) 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 A beta 42 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 A beta 42, the concentration of A beta 42 in solution phase, and the presence of Fe3+ ions on A beta 42 fibrillation. The increase in either the surface density of A beta 42 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.