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Dynamical predictors of an imminent phenotypic switch in bacteria
Huijing Wang1, J Christian J Ray1,2,3
1Center for Computational Biology, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, United States of America.
Physical Biology
|June 10, 2017
Summary
Metabolic flickering, a pattern of rapid fluctuations, can predict critical state changes in bacterial regulatory networks. This early warning signal helps anticipate transitions caused by enzyme saturation.
Area of Science:
- Systems Biology
- Biophysics
- Metabolic Engineering
Background:
- Single cells exhibit stochastic switching across regulatory network thresholds, acting as tipping points for drastic phenotypic state changes.
- Dynamical early warning indicators, such as 'flickering' of fast variables, can predict imminent transitions across tipping points in ecological and economic systems.
Purpose of the Study:
- To investigate if metabolic early warning indicators, specifically 'flickering,' can predict imminent phenotypic transitions in bacteria caused by enzyme saturation.
- To explore the influence of various molecular and physiological parameters on the predictive power of metabolic flickering.
Main Methods:
- Stochastic simulations were employed to model bacterial metabolic and regulatory networks.
- The study accounted for parameters including enzyme affinity, gene expression burstiness, homeostatic feedback, and precursor influx rates.
Main Results:
- Metabolic flickering rates were found to be robustly peaked near the enzyme saturation threshold, indicating a predictive signal.
- Product inhibition of enzymes amplified the degree of metabolic fluctuation.
- Flickering effectively predicted phenotypic transitions across a range of simulated conditions.
Conclusions:
- Metabolic flickering serves as a reliable early warning indicator for imminent phenotypic transitions in bacterial cells.
- Sensitivity to metabolic flickering may represent a natural or synthetic strategy for preparing physiological states for critical transitions.
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