Mechanical manipulation of Alzheimer's amyloid beta1-42 fibrils.
The 39- to 42-residue-long amyloid beta-peptide (Abeta-peptide) forms filamentous structures in the neuritic plaques found in the neuropil of Alzheimer's disease patients. The assembly and deposition of Abeta-fibrils is one of the most important factors in the pathogenesis of this neurodegenerative disease. Although the structural analysis of amyloid fibrils is difficult, single-molecule methods may provide unique insights into their characteristics. In the present work, we explored the nanomechanical properties of amyloid fibrils formed from the full-length, most neurotoxic Abeta1-42 peptide, by manipulating individual fibrils with an atomic force microscope. We show that Abeta-subunit sheets can be mechanically unzipped from the fibril surface with constant forces in a reversible transition. The fundamental unzipping force (approximately 23 pN) was significantly lower than that observed earlier for fibrils formed from the Abeta1-40 peptide (approximately 33 pN), suggesting that the presence of the two extra residues (Ile and Ala) at the peptide's C-terminus result in a mechanical destabilization of the fibril. Deviations from the constant force transition may arise as a result of geometrical constraints within the fibril caused by its left-handed helical structure. The nanomechanical fingerprint of the Abeta1-42 is further influenced by the structural dynamics of intrafibrillar interactions.
Karsai
A
A
Department of Biophysics, University of Pécs, Faculty of Medicine, Pécs H-7624, Hungary.
Mártonfalvi
Zs
Z
Nagy
A
A
Grama
L
L
Penke
B
B
Kellermayer
M S Z
MS
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D004548:Elasticity; D006801:Humans; D018625:Microscopy, Atomic Force / Q000379:methods; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)