Structural and nanomechanical comparison of epitaxially and solution-grown amyloid β25-35 fibrils

Abstract

Aβ25-35, the fibril-forming, biologically active toxic fragment of the full-length amyloid β-peptide also forms fibrils on mica by an epitaxial assembly mechanism. Here we investigated, by using atomic force microscopy, nanomechanical manipulation and FTIR spectroscopy, whether the epitaxially grown fibrils display structural and mechanical features similar to the ones evolving under equilibrium conditions in bulk solution. Unlike epitaxially grown fibrils, solution-grown fibrils displayed a heterogeneous morphology and an apparently helical structure. While fibril assembly in solution occurred on a time scale of hours, it appeared within a few minutes on mica surface fibrils. Both types of fibrils showed a similar plateau-like nanomechanical response characterized by the appearance of force staircases. The IR spectra of both fibril types contained an intense peak between 1620 and 1640 cm(-1), indicating that β-sheets dominate their structure. A shift in the amide I band towards greater wave numbers in epitaxially assembled fibrils suggests that their structure is less compact than that of solution-grown fibrils. Thus, equilibrium conditions are required for a full structural compaction. Epitaxial Aβ25-35 fibril assembly, while significantly accelerated, may trap the fibrils in less compact configurations. Considering that under in vivo conditions the assembly of amyloid fibrils is influenced by the presence of extracellular matrix components, the ultimate fibril structure is likely to be influenced by the features of underlying matrix elements.

Keywords: Amyloid; Atomic force microscopy; Force spectroscopy; Fourier transform infrared spectroscopy; Structural compaction; β-Sheet structure.