The role of dynamic stimulation pattern in the analysis of bistable intracellular networks

Thomas Millat, Sree N. Sreenath, Radina P. Soebiyanto, Jayant Avva, Kwang Hyun Cho, Olaf Wolkenhauer

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Bistable systems play an important role in the functioning of living cells. Depending on the strength of the necessary positive feedback one can distinguish between (irreversible) "one-way switch" or (reversible) "toggle-switch" type behavior. Besides the well- established steady-state properties, some important characteristics of bistable systems arise from an analysis of their dynamics. We demonstrate that a supercritical stimulus amplitude is not sufficient to move the system from the lower (off-state) to the higher branch (on-state) for either a step or a pulse input. A switching surface is identified for the system as a function of the initial condition, input pulse amplitude and duration (a supercritical signal). We introduce the concept of bounded autonomy for single level systems with a pulse input. Towards this end, we investigate and characterize the role of the duration of the stimulus. Furthermore we show, that a minimal signal power is also necessary to change the steady state of the bistable system. This limiting signal power is independent of the applied stimulus and is determined only by systems parameters. These results are relevant for the design of experiments, where it is often difficult to create a defined pattern for the stimulus. Furthermore, intracellular processes, like receptor internalization, do manipulate the level of stimulus such that level and duration of the stimulus is conducive to characteristic behavior.

Original languageEnglish (US)
Pages (from-to)270-281
Number of pages12
JournalBioSystems
Volume92
Issue number3
DOIs
StatePublished - Jun 2008
Externally publishedYes

Fingerprint

Bistable System
Switches
duration
Design of experiments
Switch
Cells
autonomy
Feedback
Positive Feedback
Necessary
Design of Experiments
experimental design
Receptor
receptors
Branch
Initial conditions
Limiting
Sufficient
analysis
Cell

Keywords

  • Bounded autonomy
  • Cell signalling
  • Multistability
  • Systems biology
  • Transient behavior

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Biotechnology
  • Drug Discovery

Cite this

Millat, T., Sreenath, S. N., Soebiyanto, R. P., Avva, J., Cho, K. H., & Wolkenhauer, O. (2008). The role of dynamic stimulation pattern in the analysis of bistable intracellular networks. BioSystems, 92(3), 270-281. https://doi.org/10.1016/j.biosystems.2008.03.007

The role of dynamic stimulation pattern in the analysis of bistable intracellular networks. / Millat, Thomas; Sreenath, Sree N.; Soebiyanto, Radina P.; Avva, Jayant; Cho, Kwang Hyun; Wolkenhauer, Olaf.

In: BioSystems, Vol. 92, No. 3, 06.2008, p. 270-281.

Research output: Contribution to journalArticle

Millat, T, Sreenath, SN, Soebiyanto, RP, Avva, J, Cho, KH & Wolkenhauer, O 2008, 'The role of dynamic stimulation pattern in the analysis of bistable intracellular networks', BioSystems, vol. 92, no. 3, pp. 270-281. https://doi.org/10.1016/j.biosystems.2008.03.007
Millat, Thomas ; Sreenath, Sree N. ; Soebiyanto, Radina P. ; Avva, Jayant ; Cho, Kwang Hyun ; Wolkenhauer, Olaf. / The role of dynamic stimulation pattern in the analysis of bistable intracellular networks. In: BioSystems. 2008 ; Vol. 92, No. 3. pp. 270-281.
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