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Delay-induced anomalous fluctuations in intracellular regulation
Andreas Grönlund1, Per Lötstedt, Johan Elf
1Department of Mathematics, Uppsala University, SE-751 06 Uppsala, Sweden.
Nature Communications
|August 11, 2011
Summary
Negative feedback typically stabilizes systems, but delays in intracellular processes like transcription can unexpectedly increase molecular fluctuations. This study reveals how delayed negative feedback impacts cellular control mechanisms.
Area of Science:
- Systems Biology
- Biophysics
- Molecular Biology
Background:
- Homeostatic control relies on negative feedback to minimize fluctuations.
- Intracellular regulation often involves indirect mechanisms with inherent delays, such as multistep synthesis pathways (e.g., transcription, translation).
Purpose of the Study:
- To derive an analytical expression quantifying the impact of delayed negative feedback on molecular fluctuations in biological systems.
- To understand the design principles of delayed stochastic control and the effects of feedback delay distribution.
Main Methods:
- Analytical derivation of mathematical expressions.
- Modeling of multistep synthesis pathways with delayed negative feedback.
- Analysis of stochastic control systems.
Main Results:
- Delayed negative feedback can increase molecular fluctuations for intermediate delays, contrary to direct feedback.
- These increased fluctuations arise from positive correlations in delayed regulatory events, equivalent to increased molecular synthesis stoichiometry.
- Long delays do not necessarily lead to increased fluctuations.
Conclusions:
- Feedback delay significantly influences the stability and fluctuations of intracellular regulatory processes.
- Understanding feedback delay is crucial for designing robust biological control systems.
- Delayed feedback in auto-repressed systems can enhance regulatory sensitivity through stochastic focusing.
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