Fig. 2

Well-tempered controller (WTC) circuit. A Schematic representation of the circuit structure and its parametrization. Rectangles: genes with associated promoters; ellipses: proteins (corresponding color); lines with arrows: molecular reactions; lines with bar heads: regulatory interactions for inactivation. B Experimental and simulated aTc dose-response curve for the WTC. Blue: mean (circles) and standard deviation (error bars) of experimental data obtained by flow cytometry; green line: simulation results for the estimated parameter values in Table 1. Additionally, we used estimated values \(d_{C} = 0.006 \text { min}^{-1}\), \(d_{Tet} = 0.0087 \text { min}^{-1}\), \(\theta _{Tet} = 0.006 \text { nM}\), and \(\theta _{Tup} = 0.5 \cdot 10^{-4} \text { nM}\). To match the model output (Citrine concentration) to fluorescence (a.u.), we determined a scaling factor as in [4]. C Simulated dose-response curves of a population of cells for a given population parameter \(\gamma\) with a coefficient of variation \(CV \approx 10\%\). Parameter means were the estimated parameters from (B). Blue line: mean response; gray lines: responses of individual cells; black line: reference linear dose-response curve; red lines: reference curve \(\pm \varepsilon = 6\,\textrm{nM}\); the individual cost threshold; an individual trajectory is viable if it lies within the red curves on average. Note that aTc is in linear scale