title: Shear flow induces amyloid fibril formation.
abstract: Shear flow is indirectly implicated in amyloid formation in vitro. Despite the association between amyloid fibrils and disease, and the prevalence of flow in physiological systems, the effect of this parameter is uncharacterized. We designed a novel Couette cell to quantitatively investigate shear exposure during fibrillogenesis. Amyloid formation by beta-lactoglobulin was monitored in situ with real-time fluorescence measurements across a range of shear rates. We demonstrate shear-induced aggregation of spheroidal seed-like species. These seeds enhance fibril formation in native beta-lactoglobulin, thereby demonstrating that shear flow generates an amyloidogenic precursor. Furthermore, preformed fibrils are degraded by exposure to high shear rates. Our results have implications for the mechanism of amyloid formation in physiological flow conditions.
authors.affiliation: Department of Chemical & Biomolecular Engineering and Department of Biochemistry & Molecular Biology, University of Melbourne, Victoria 3010, Australia.
authors.forename: Elisabeth K
authors.initials: EK
authors.lastname: Hill
authors.forename: Benjamin
authors.initials: B
authors.lastname: Krebs
authors.forename: Dianna G
authors.initials: DG
authors.lastname: Goodall
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Howlett
authors.forename: Dave E
authors.initials: DE
authors.lastname: Dunstan
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D000686:Amyloidosis; D000818:Animals; D052160:Benzothiazoles; D002417:Cattle; D007782:Lactoglobulins / Q000737:chemistry / Q000378:metabolism; D018625:Microscopy, Atomic Force; D020836:Protein Structure, Quaternary; D012212:Rheology; D013050:Spectrometry, Fluorescence; D013844:Thiazoles
chemical_list: D000682:Amyloid; D052160:Benzothiazoles; D007782:Lactoglobulins; D013844:Thiazoles; C009462:thioflavin T