title: Amyloid fibril length distribution quantified by atomic force microscopy single-particle image analysis.
abstract: Amyloid fibrils are proteinaceous nano-scale linear aggregates. They are of key interest not only because of their association with numerous disorders, such as type II diabetes mellitus, Alzheimer's and Parkinson's diseases, but also because of their potential to become engineered high-performance nano-materials. Methods to characterise the length distribution of nano-scale linear aggregates such as amyloid fibrils are of paramount importance both in understanding the biological impact of these aggregates and in controlling their mechanical properties as potential nano-materials. Here, we present a new quantitative approach to the determination of the length distribution of amyloid fibrils using tapping-mode atomic force microscopy. The method described employs single-particle image analysis corrected for the length-dependent bias that is a common problem associated with surface-based imaging techniques. Applying this method, we provide a detailed characterisation of the length distribution of samples containing long-straight fibrils formed in vitro from beta(2)-microglobulin. The results suggest that the Weibull distribution is a suitable model in describing fibril length distributions, and reveal that fibril fragmentation is an important process even under unagitated conditions. These results demonstrate the significance of quantitative length distribution measurements in providing important new information regarding amyloid assembly.
authors: Astbury Centre for Structural Molecular Biology, Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS29JT, UK. w.f.xue@leeds.ac.uk
authors: Wei-Feng
authors: WF
authors: Xue
authors: Steve W
authors: SW
authors: Homans
authors: Sheena E
authors: SE
authors: Radford
mesh_terms: D000465:Algorithms; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016018:Least-Squares Analysis; D018625:Microscopy, Atomic Force / Q000379:methods*; D018709:Statistics, Nonparametric
chemical_list: D000682:Amyloid