An Imaging and Systems Modeling Approach to Fibril Breakage Enables Prediction of Amyloid Behavior

Xue, Wei-Feng, Radford, Sheena E. (2013) An Imaging and Systems Modeling Approach to Fibril Breakage Enables Prediction of Amyloid Behavior. Biophysical Journal, 105 (12). pp. 2811-2819. ISSN 0006-3495. (doi:10.1016/j.bpj.2013.10.034)

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 ?2-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.

Item Type: Article
DOI/Identification number: 10.1016/j.bpj.2013.10.034
Subjects: Q Science
Q Science > QC Physics
Q Science > QD Chemistry
Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Wei-Feng Xue
Date Deposited: 22 Dec 2013 11:50 UTC
Last Modified: 29 May 2019 11:42 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/37690 (The current URI for this page, for reference purposes)
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