title: Quantitative morphological analysis reveals ultrastructural diversity of amyloid fibrils from alpha-synuclein mutants.
abstract: High resolution atomic force microscopy is a powerful tool to characterize nanoscale morphological features of protein amyloid fibrils. Comparison of fibril morphological properties between studies has been hampered by differences in analysis procedures and measurement error determination used by various authors. We describe a fibril morphology analysis method that allows for quantitative comparison of features of amyloid fibrils of any amyloidogenic protein measured by atomic force microscopy. We have used tapping mode atomic force microscopy in liquid to measure the morphology of fibrillar aggregates of human wild-type alpha-synuclein and the disease-related mutants A30P, E46K, and A53T. Analysis of the images shows that fibrillar aggregates formed by E46K alpha-synuclein have a smaller diameter (9.0 +/- 0.8 nm) and periodicity (mode at 55 nm) than fibrils of wild-type alpha-synuclein (height 10.0 +/- 1.1 nm; periodicity has a mode at 65 nm). Fibrils of A30P have smaller diameter still (8.1 +/- 1.2 nm) and show a variety of periodicities. This quantitative analysis procedure enables comparison of the results with existing models for assembly of amyloid fibrils.
authors.affiliation: MESA+ Institute for Nanotechnology, Faculty of Science and Technology, University of Twente, 7500 AE, Enschede, The Netherlands.
authors.forename: Martijn E
authors.initials: ME
authors.lastname: van Raaij
authors.forename: Ine M J
authors.initials: IM
authors.lastname: Segers-Nolten
authors.forename: Vinod
authors.initials: V
authors.lastname: Subramaniam
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure*; D001703:Biophysics / Q000379:methods*; D006801:Humans; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D009154:Mutation; D053758:Nanoparticles; D036103:Nanotechnology / Q000379:methods; D013696:Temperature; D013997:Time Factors; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D000682:Amyloid; D051844:alpha-Synuclein