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

Meisl, Georg; Rajah, Luke; Cohen, Samuel I A; Pfammatter, Manuela; Šarić, Andela; Hellstrand, Erik LU ; Buell, Alexander K.; Aguzzi, Adriano; Linse, Sara LU and Vendruscolo, Michele, et al. (2017) In Chemical Science 8(10). p.7087-7097
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... (More)

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.

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published
subject
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Chemical Science
volume
8
issue
10
pages
11 pages
publisher
Royal Society of Chemistry
external identifiers
  • scopus:85030099585
  • wos:000411730500045
ISSN
2041-6520
DOI
10.1039/c7sc01965c
language
English
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yes
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e97f4858-d0a3-4ccc-b3e9-435374561462
date added to LUP
2017-10-10 12:06:15
date last changed
2018-07-22 04:29:39
@article{e97f4858-d0a3-4ccc-b3e9-435374561462,
  abstract     = {<p>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.</p>},
  author       = {Meisl, Georg and Rajah, Luke and Cohen, Samuel I A and Pfammatter, Manuela and Šarić, Andela and Hellstrand, Erik and Buell, Alexander K. and Aguzzi, Adriano and Linse, Sara and Vendruscolo, Michele and Dobson, Christopher M and Knowles, Tuomas P J},
  issn         = {2041-6520},
  language     = {eng},
  number       = {10},
  pages        = {7087--7097},
  publisher    = {Royal Society of Chemistry},
  series       = {Chemical Science},
  title        = {Scaling behaviour and rate-determining steps in filamentous self-assembly},
  url          = {http://dx.doi.org/10.1039/c7sc01965c},
  volume       = {8},
  year         = {2017},
}