Stability of bacterial toggle switches is enhanced by cell-cycle lengthening by several orders of magnitude
Bistable regulatory elements are important for nongenetic inheritance, increase of cell-to-cell heterogeneity allowing adaptation, and robust responses at the population level. Here, we study computationally the bistable genetic toggle switch-a small regulatory network consisting of a pair of mutual repressors-in growing and dividing bacteria. We show that as cells with an inhibited growth exhibit high stability of toggle states, cell growth and divisions lead to a dramatic increase of toggling rates. The toggling rates were found to increase with rate of cell growth, and can be up to six orders of magnitude larger for fast growing cells than for cells with the inhibited growth. The effect is caused mainly by the increase of protein and mRNA burst sizes associated with the faster growth. The observation that fast growth dramatically destabilizes toggle states implies that rapidly growing cells may vigorously explore the epigenetic landscape enabling nongenetic evolution, while cells with inhibited growth adhere to the local optima. This can be a clever population strategy that allows the slow growing (but stress resistant) cells to survive long periods of unfavorable conditions. Simultaneously, at favorable conditions, this stress resistant (but slowly growing?or not growing) subpopulation may be replenished due to a high switching rate from the fast growing population.