Issue 10, 2017

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

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.

Graphical abstract: Scaling behaviour and rate-determining steps in filamentous self-assembly

Supplementary files

Article information

Article type
Edge Article
Submitted
02 may. 2017
Accepted
31 jul. 2017
First published
31 ago. 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2017,8, 7087-7097

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

G. Meisl, L. Rajah, S. A. I. Cohen, M. Pfammatter, A. Šarić, E. Hellstrand, A. K. Buell, A. Aguzzi, S. Linse, M. Vendruscolo, C. M. Dobson and T. P. J. Knowles, Chem. Sci., 2017, 8, 7087 DOI: 10.1039/C7SC01965C

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