title: Nanoscale Structure and Spectroscopic Probing of Aβ1-40 Fibril Bundle Formation.
abstract: Amyloid plaques composed of fibrillar Amyloid-β (Aβ) are hallmarks of Alzheimer's disease. However, Aβ fibrils are morphologically heterogeneous. Conformation sensitive luminescent conjugated oligothiophenes (LCOs) are versatile tools for monitoring such fibril polymorphismin vivoandin vitro. Biophysical methods applied onin vitrogenerated Aβ fibrils, stained with LCOs with different binding and fluorescence properties, can be used to characterize the Aβ fibrillation in depth, far beyond that possible forin vivogenerated amyloid plaques. In this study,in vitrofibrillation of the Aβ1-40 peptide was monitored by time-lapse transmission electron microscopy, LCO fluorescence, and atomic force microscopy. Differences in the LCO binding in combination with nanoscale imaging revealed that spectral variation correlated with fibrils transforming from solitary filaments (Ø~2.5 nm) into higher order bundled structures (Ø~5 nm). These detailedin vitroexperiments can be used to derive data that reflects the heterogeneity ofin vivogenerated Aβ plaques observed by LCO fluorescence. Our work provides new structural basis for targeted drug design and molecular probe development for amyloid imaging.
authors.affiliation: Department of Physics, Norwegian University of Science and Technology NTNU Trondheim, Norway.
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Psonka-Antonczyk
authors.affiliation: IFM-Department of Chemistry, Linköping University Linköping, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Hammarström
authors.affiliation: IFM-Department of Chemistry, Linköping University Linköping, Sweden.
authors.forename: Leif B G
authors.initials: LB
authors.lastname: Johansson
authors.affiliation: Department of Physics, Norwegian University of Science and Technology NTNUTrondheim, Norway; IFM-Department of Chemistry, Linköping UniversityLinköping, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Lindgren
authors.affiliation: Department of Physics, Norwegian University of Science and Technology NTNU Trondheim, Norway.
authors.forename: Bjørn T
authors.initials: BT
authors.lastname: Stokke
authors.affiliation: IFM-Department of Chemistry, Linköping University Linköping, Sweden.
authors.forename: K Peter R
authors.initials: KP
authors.lastname: Nilsson
authors.affiliation: IFM-Department of Chemistry, Linköping University Linköping, Sweden.
authors.forename: Sofie
authors.initials: S
authors.lastname: Nyström
keywords: AFM; SPR; amyloid formation; amyloids; fibrillation; hyperspectral imaging; oligothiophenes