title: Surface effects mediate self-assembly of amyloid-β peptides.
abstract: Here we present a label-free method for studying the mechanism of surface effects on amyloid aggregation. In this method, spin-coating is used to rapidly dry samples, in a homogeneous manner, after various incubation times. This technique allows the control of important parameters for self-assembly, such as the surface concentration. Atomic force microscopy is then used to obtain high-resolution images of the morphology. While imaging under dry conditions, we show that the morphologies of self-assembled aggregates of a model amyloid-β peptide, Aβ(12-28), are strongly influenced by the local surface concentration. On mica surfaces, where the peptides can freely diffuse, homogeneous, self-assembled protofibrils formed spontaneously and grew longer with longer subsequent incubation. The surface fibrillization rate was much faster than the rates of fibril formation observed in solution, with initiation occurring at much lower concentrations. These data suggest an alternative pathway for amyloid formation on surfaces where the nucleation stage is either bypassed entirely or too fast to measure. This simple preparation procedure for high-resolution atomic force microscopy imaging of amyloid oligomers and protofibrils should be applicable to any amyloidogenic protein species.
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Yi-Chih
authors.initials: YC
authors.lastname: Lin
authors.forename: E James
authors.initials: EJ
authors.lastname: Petersson
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fakhraai
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D016229:Amyloid beta-Peptides; D010455:Peptides
keywords: Aβ; amyloids; fibrils; protofibrils; surface-mediated self-assembly