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Scaling behaviour and rate-determining steps in filamentous self-assembly

Meisl, G; Rajah, L; Cohen, SAI; Pfammatter, M; Šarić, A; Hellstrand, E; Buell, AK; ... Knowles, TPJ; + view all (2017) Scaling behaviour and rate-determining steps in filamentous self-assembly. Chem. Sci. 10.1039/C7SC01965C. (In press). Green open access

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Abstract

The formation of filaments from naturally occurring protein molecules is a process at the core of a range of functional and aberrant biological phenomena, such as the assembly of the cytoskeleton or the appearance of aggregates in Alzheimer's disease. The macroscopic behaviour associated with such processes is remarkably diverse, ranging from simple nucleated growth to highly cooperative processes with a well-defined lagtime. Thus, conventionally, different molecular mechanisms have been used to explain the self-assembly of different proteins. Here we show that this range of behaviour can be quantitatively captured by a single unifying Petri net that describes filamentous growth in terms of aggregate number and aggregate mass concentrations. By considering general features associated with a particular network connectivity, we are able to establish directly the rate-determining steps of the overall aggregation reaction from the system's scaling behaviour. We illustrate the power of this framework on a range of different experimental and simulated aggregating systems. The approach is general and will be applicable to any future extensions of the reaction network of filamentous self-assembly.

Type: Article
Title: Scaling behaviour and rate-determining steps in filamentous self-assembly
Open access status: An open access version is available from UCL Discovery
DOI: 10.1039/C7SC01965C
Publisher version: http://dx.doi.org/10.1039/C7SC01965C
Language: English
Additional information: Open Access Article. Published on 31 August 2017. Downloaded on 04/09/2017 10:12:59. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy
URI: https://discovery.ucl.ac.uk/id/eprint/1572224
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