Abstract Unicellular organisms adapt to their changing environments by gene regulatory switches that sense chemical cues and induce specific target genes when the inducing signal is over a critical threshold. Using mathematical modeling we here show that, because growth rate sets the dilution rate of intra-cellular molecules, the sensitivity of gene regulatory switches generally decreases with growth rate, independent of their precise architecture. We confirm the modeling predictions by experimentally demonstrating that the concentration of inducer required for activating the lac operon in E. coli decreases quadratically with growth rate at the population level, and that growth-arrested cells become hyper-sensitive to inducer at the single-cell level. Moreover, we establish that this growth-coupled sensitivity allows bacteria to implement concentration-dependent sugar preferences, in which a new carbon source is used only if its concentration is high enough to improve upon the current growth rate of the cells. Using microfluidics in combination with time-lapse microscopy, we validate experimentally that this strategy governs how mixtures of glucose and lactose are used in E. coli and that the central regulator CRP plays a key role in implementing this strategy. Overall growth-coupled sensitivity provides a general mechanism through which cells can ‘mute’ external signals in beneficial conditions when growth is fast, and become highly sensitive to alternative nutrients or stresses when growth is slow or arrested.

Growth rate controls the sensitivity of gene regulatory circuits