Reversible mechanical unzipping of amyloid β-fibrils

Abstract

Amyloid fibrils are self-associating filamentous structures, the deposition of which is considered to be one of the most important factors in the pathogenesis of Alzheimer's disease and various other disorders. Here we used single molecule manipulation methods to explore the mechanics and structural dynamics of amyloid fibrils. In mechanically manipulated amyloid fibrils, formed from either amyloid β (Aβ) peptides 1-40 or 25-35, β-sheets behave as elastic structures that can be "unzipped" from the fibril with constant forces. The unzipping forces were different for Aβ1-40 and Aβ25-35. Unzipping was fully reversible across a wide range of stretch rates provided that coupling, via the β-sheet, between bound and dissociated states was maintained. The rapid, cooperative zipping together of β-sheets could be an important mechanism behind the self-assembly of amyloid fibrils. The repetitive force patterns contribute to a mechanical fingerprint that could be utilized in the characterization of different amyloid fibrils. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.