Cellular Growth Arrest and Persistence from Enzyme Saturation
Fig 2
Predicted population growth rates for varying substrate import rates in simulated metabolic pathway models.
(A) Average single cell growth rates predicted with a stochastic model (N = 10,000 trajectories) with substrate toxicity. Intracellular metabolite production rates are controlled by changing the transcription rate of Enzyme A (ktA). The discrepancy with experimentally measured growth rates at high metabolite concentrations (Fig 3a) are discussed in Methods. (B) Correlations between single-cell molecule numbers and growth rates reveal mechanisms of growth arrest in stochastic simulations. Positive correlations imply that the molecule species improves growth, while negative correlations imply the opposite. The black dashed line indicates the parameter value predicted to give peak growth rate. Correlations where all trajectories enter growth arrest (making model predictions irrelevant) are not shown. (C) Predicted population densities (color bar) of cellular growth rate and metabolite from stochastic simulations in the low toxicity case. All trajectories in these three cases start with low metabolite concentrations. As the simulations proceed, trajectories exceeding a threshold concentration of metabolite transition from the low-metabolite subpopulation to the high-metabolite subpopulation. The predicted growth rate of the high-metabolite subpopulation decreases as metabolite continues to build up.