title: Effect of the beta-sheet-breaker peptide LPFFD on oriented network of amyloid β25-35 fibrils.
abstract: Amyloid fibrils are self-associating filamentous structures deposited in extracellular tissue in various neurodegenerative and protein misfolding disorders. It has been shown that beta-sheet-breaker (BSB) peptides may interfere with amyloid fibril assembly. Although BSB peptides are prospective therapeutic agents in amyloidosis, there is ambiguity about the mechanisms and generality of their action. In the present work we analyzed the effect of the BSB peptide LPFFD on the growth kinetics, morphologic, and mechanical properties of amyloid β25-35 (Aβ25-35) fibrils assembled in an oriented array on mica surface. Aβ25-35 is thought to represent the biologically active, toxic fragment of the full-length Aβ peptide. Growth kinetics and morphologic features were analyzed using in situ atomic force microscopy in the presence of various concentrations of LPFFD. We found that the addition of LPFFD only slightly altered the assembly kinetics of Aβ25-35 fibrils. Already formed fibrils did not disassemble in the presence of high concentrations of LPFFD. The mechanical stability of the fibrils was explored with force spectroscopy methods. The nanomechanical behavior of Aβ25-35 fibrils is characterized by the appearance of force staircases which correspond to the force-driven unzipping and dissociation of several protofilaments. In the presence of LPFFD single-plateau force traces dominated. The effects of LPFFD on Aβ25-35 fibril assembly and stability suggest that inter-protofilament interactions were slightly weakened. Complete disassembly of fibrils, however, was not observed. Thus, under the conditions explored here, LPFFD may not be considered as a BSB peptide with generalized beta-sheet breaking properties.
authors.affiliation: Department of Biophysics and Radiation Biology, Semmelweis University, Tűzoltó u. 37-47, Budapest H-1094, Hungary.
authors.forename: Unige
authors.initials: U
authors.lastname: Murvai
authors.forename: Katalin
authors.initials: K
authors.lastname: Soós
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.forename: Miklós S Z
authors.initials: MS
authors.lastname: Kellermayer
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010455:Peptides; C074636:amyloid beta-protein (25-35); C474023:iAbeta5 peptide