Skip Navigation


PEDS Advance Access originally published online on July 6, 2009
Protein Engineering Design and Selection 2009 22(8):489-496; doi:10.1093/protein/gzp026
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
22/8/489    most recent
gzp026v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Xue, W.-F.
Right arrow Articles by Radford, S. E.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xue, W.-F.
Right arrow Articles by Radford, S. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

This article appears in the following Protein Engineering issue: Amyloids Special Issue [View the issue table of contents]

Amyloid fibril length distribution quantified by atomic force microscopy single-particle image analysis

Wei-Feng Xue1, Steve W. Homans and Sheena E. Radford1

Astbury Centre for Structural Molecular Biology, Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK

1 To whom correspondence should be addressed. E-mail: w.f.xue{at}leeds.ac.uk, s.e.radford{at}leeds.ac.uk

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 β2-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.

Keywords: bias correction/brittleness/fibril fragmentation/single-molecule method/size distribution

Received May 27, 2009; revised May 27, 2009; accepted June 3, 2009.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.