title: FRET evidence for untwisting of amyloid fibrils on the surface of model membranes.
abstract: Apolipoprotein A-I (apoA-I) is an amyloid-forming protein whose amyloidogenic properties are attributed mainly to its N-terminal fragment. Cell membranes are thought to be the primary target for the toxic amyloid aggregates. In the present study Förster resonance energy transfer (FRET) between the membrane fluorescent probe Laurdan as a donor and amyloid-specific dye Thioflavin T (ThT) as an acceptor was employed to explore the interactions of amyloid fibrils from apoA-I variants 1-83/G26R and 1-83/G26R/W@8 with the model membranes composed of phosphatidylcholine and its mixture with cholesterol. The changes in FRET efficiency upon fibril-lipid binding were found to correlate with the extent of protein fibrillization. AFM imaging revealed the presence of two polymorphic states of fibrillar 1-83/G26R/W@8 with the helical and twisted ribbon morphologies. The simulation-based analysis of the experimental FRET profiles provided the arguments in favor of untwisting of fibrillar assemblies upon their interaction with the model membranes. Evidence for the face-on orientation and superficial bilayer location of the membrane-bound fragments of 1-83/G26R/W@8 fibrils was obtained.
authors.affiliation: Department of Nuclear and Medical Physics, V.N. Karazin Kharkiv National University, 4 Svobody Sq., Kharkov, 61022, Ukraine. galyagor@yahoo.com.
authors.forename: Galyna
authors.initials: G
authors.lastname: Gorbenko
authors.forename: Valeriya
authors.initials: V
authors.lastname: Trusova
authors.forename: Mykhailo
authors.initials: M
authors.lastname: Girych
authors.forename: Emi
authors.initials: E
authors.lastname: Adachi
authors.forename: Chiharu
authors.initials: C
authors.lastname: Mizuguchi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Akaji
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Saito
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008567:Membranes, Artificial
chemical_list: D000682:Amyloid; D016632:Apolipoprotein A-I; D008567:Membranes, Artificial