by Beil, Michael, Lück, Sebastian, Fleischer, Frank, Portet, Stéphanie, Arendt, Wolfgang and Schmidt, Volker
Abstract:
Keratin intermediate filament networks are part of the cytoskeleton in epithelial cells. They were found to regulate viscoelastic properties and motility of cancer cells. Due to unique biochemical properties of keratin polymers, the knowledge of the mechanisms controlling keratin network formation is incomplete. A combination of deterministic and stochastic modeling techniques can be a valuable source of information since they can describe known mechanisms of network evolution while reflecting the uncertainty with respect to a variety of molecular events. We applied the concept of piecewise-deterministic Markov processes to the modeling of keratin network formation with high spatiotemporal resolution. The deterministic component describes the diffusion-driven evolution of a pool of soluble keratin filament precursors fueling various network formation processes. Instants of network formation events are determined by a stochastic point process on the time axis. A probability distribution controlled by model parameters exercises control over the frequency of different mechanisms of network formation to be triggered. Locations of the network formation events are assigned dependent on the spatial distribution of the soluble pool of filament precursors. Based on this modeling approach, simulation studies revealed that the architecture of keratin networks mostly depends on the balance between filament elongation and branching processes. The spatial distribution of network mesh size, which strongly influences the mechanical characteristics of filament networks, is modulated by lateral annealing processes. This mechanism which is a specific feature of intermediate filament networks appears to be a major and fast regulator of cell mechanics.
Reference:
Simulating the formation of keratin filament networks by a piecewise-deterministic Markov process (Beil, Michael, Lück, Sebastian, Fleischer, Frank, Portet, Stéphanie, Arendt, Wolfgang and Schmidt, Volker), In Journal of Theoretical Biology, volume 256, 2009.
Bibtex Entry:
@ARTICLE{Beil2009,
author = {Beil, Michael and Lück, Sebastian and Fleischer, Frank and Portet,
St\'ephanie and Arendt, Wolfgang and Schmidt, Volker},
title = {Simulating the formation of keratin filament networks by a piecewise-deterministic
Markov process},
journal = {Journal of Theoretical Biology},
year = {2009},
volume = {256},
pages = {518--532},
number = {4},
month = {Feb},
abstract = {Keratin intermediate filament networks are part of the cytoskeleton
in epithelial cells. They were found to regulate viscoelastic properties
and motility of cancer cells. Due to unique biochemical properties
of keratin polymers, the knowledge of the mechanisms controlling
keratin network formation is incomplete. A combination of deterministic
and stochastic modeling techniques can be a valuable source of information
since they can describe known mechanisms of network evolution while
reflecting the uncertainty with respect to a variety of molecular
events. We applied the concept of piecewise-deterministic Markov
processes to the modeling of keratin network formation with high
spatiotemporal resolution. The deterministic component describes
the diffusion-driven evolution of a pool of soluble keratin filament
precursors fueling various network formation processes. Instants
of network formation events are determined by a stochastic point
process on the time axis. A probability distribution controlled by
model parameters exercises control over the frequency of different
mechanisms of network formation to be triggered. Locations of the
network formation events are assigned dependent on the spatial distribution
of the soluble pool of filament precursors. Based on this modeling
approach, simulation studies revealed that the architecture of keratin
networks mostly depends on the balance between filament elongation
and branching processes. The spatial distribution of network mesh
size, which strongly influences the mechanical characteristics of
filament networks, is modulated by lateral annealing processes. This
mechanism which is a specific feature of intermediate filament networks
appears to be a major and fast regulator of cell mechanics.},
doi = {10.1016/j.jtbi.2008.09.044},
institution = {Department of Internal Medicine I, University Hospital Ulm, D-89070
Ulm, Germany. michael.beil@uni-ulm.de},
keywords = {Algorithms; Animals; Diffusion; Intermediate Filaments, metabolism/ultrastructure;
Keratins, biosynthesis/ultrastructure; Markov Chains; Metabolic Networks
and Pathways, physiology; Microscopy, Electron, Scanning; Models,
Biological},
language = {eng},
medline-pst = {ppublish},
owner = {sportet},
pii = {S0022-5193(08)00504-3},
pmid = {19014958},
timestamp = {2013.11.13},
url = {http://dx.doi.org/10.1016/j.jtbi.2008.09.044}
}