Title
The role of dynamic stimulation pattern in the analysis of bistable intracellular networks.
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.
Year
DOI
Venue
2008
10.1016/j.biosystems.2008.03.007
Biosystems
Keywords
Field
DocType
Systems biology,Cell signalling,Multistability,Transient behavior,Bounded autonomy
Bistability,Control theory,Computer science,Negative feedback,Positive feedback,Pulse (signal processing),Stimulus (physiology),Steady state,Multistability,Pulse-amplitude modulation
Journal
Volume
Issue
ISSN
92
3
0303-2647
Citations 
PageRank 
References 
2
0.62
0
Authors
6
Name
Order
Citations
PageRank
Thomas Millat1202.64
Sree N. Sreenath261.92
Radina P. Soebiyanto392.44
Jayant Avva420.62
Kwang-Hyun Cho551153.57
Olaf Wolkenhauer633040.25