Shear Flow Induces Amyloid Fibril Formation

• Published in: Biomacromolecules 2006-01, Vol.7 (1), p.10-13
• Main Authors: Hill, Elisabeth K, Krebs, Benjamin, Goodall, Dianna G, Howlett, Geoffrey J, Dunstan, Dave E
• Format: Article
• Language: English
• Subjects: Amyloid - chemistry; Amyloid - metabolism; Amyloid - ultrastructure; Amyloidosis; Animals; Applied sciences; Biological and medical sciences; Cattle; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; In solution. Condensed state. Thin layers; Lactoglobulins - chemistry; Lactoglobulins - metabolism; Microscopy, Atomic Force; Molecular biophysics; Natural polymers; Physico-chemical properties of biomolecules; Physicochemistry of polymers; Protein Structure, Quaternary; Proteins; Rheology; Spectrometry, Fluorescence; Thiazoles
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm0505078

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 β-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 β-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.