Analysis of beta-amyloid self-assembly on solid surface using atomic force microscopy and surface plasmon resonance

Abstract

Self-assembly is a process in which nanoscopic or macroscopic building blocks spontaneously form finely structured materials via weak interactions such as van der Waals interactions, hydrophobic interactions, and hydrogen bonds. With the advent and progress of nanotechnology, studies on the mechanism of self-assembly and self-assembled materials have gotten much attention because of both scientific interests and practical application. Although our attention on the self-assembly process has been gotten quite recently, self-assembly processes are utilized in many biological systems. The formation of amyloid fibrils is one of well-known examples of biological self-assembly. Amyloid fibrillation has a relevance to the etiology of various neurodegenerative diseases such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. Recently, its potential to act as a template for fabricating various nanostructures, especially various nanowires, has also attracted much interest of scientists and engineers. To date, however, the mechanism for the formation of amyloid fibrils is still unclear. This is partly due to the lack of effective analytical methods and the presence of many environmental factors affecting self-assembly process in amyloid formation. In this thesis, the formation of amyloid on solid surface was studied using atomic force microscopy (AFM) and surface plasmon resonance (SPR). The effect of metal ions such as Fe3+, Cu2+, and Zn2+ on the self-assembly of beta-amyloid (A-beta) peptides on a solid template was studied using ex-situ AFM. According to our results, the balance of metal ions such as Cu2+, Zn2+, and Fe3+ played an important role in the formation of A-beta amyloid fibrils. While Fe3+ accelerated the formation of “fibrillar” amyloids on the solid surface, Cu2+ or Zn2+ resulted in the formation of amorphous aggregates. Furthermore, we developed a SPR-based analytical system which can be effectively used for studying the self-assembly o...