Xue, W-F and Radford, SE (2013) An imaging and systems modeling approach to fibril breakage enables prediction of amyloid behavior. Biophysical Journal, 105 (12). 2811 - 2819. ISSN 0006-3495
Abstract
Delineating the nanoscale properties and the dynamic assembly and disassembly behaviors of amyloid fibrils is key for technological applications that use the material properties of amyloid fibrils, as well as for developing treatments of amyloid-associated disease. However, quantitative mechanistic understanding of the complex processes involving these heterogeneous supramolecular systems presents challenges that have yet to be resolved. Here, we develop an approach that is capable of resolving the time dependence of fibril particle concentration, length distribution, and length and position dependence of fibril fragmentation rates using a generic mathematical framework combined with experimental data derived from atomic force microscopy analysis of fibril length distributions. By application to amyloid assembly of β2-microglobulin in vitro under constant mechanical stirring, we present a full description of the fibril fragmentation and growth behavior, and demonstrate the predictive power of the approach in terms of the samples' fibril dimensions, fibril load, and their efficiency to seed the growth of new amyloid fibrils. The approach developed offers opportunities to determine, quantify, and predict the course and the consequences of amyloid assembly.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2013, Xue, W-F and Radford, SE. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 2.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 22 Sep 2014 10:16 |
Last Modified: | 02 Feb 2018 17:34 |
Published Version: | http://dx.doi.org/10.1016/j.bpj.2013.10.034 |
Status: | Published |
Publisher: | Biophysical Society |
Identification Number: | 10.1016/j.bpj.2013.10.034 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:80191 |