A Design Principle of Group-level Decision Making in Cell Populations

<div><p>Populations of cells often switch states as a group to cope with environmental changes such as nutrient availability and cell density. Although the gene circuits that underlie the switches are well understood at the level of single cells, the ways in which such circuits work in concert among many cells to support group-level switches are not fully explored. Experimental studies of microbial quorum sensing show that group-level changes in cellular states occur in either a graded or an all-or-none fashion. Here, we show through numerical simulations and mathematical analysis that these behaviors generally originate from two distinct forms of bistability. The choice of bistability is uniquely determined by a dimensionless parameter that compares the synthesis and the transport of the inducing molecules. The role of the parameter is universal, such that it not only applies to the autoinducing circuits typically found in bacteria but also to the more complex gene circuits involved in transmembrane receptor signaling. Furthermore, in gene circuits with negative feedback, the same dimensionless parameter determines the coherence of group-level transitions from quiescence to a rhythmic state. The set of biochemical parameters in bacterial quorum-sensing circuits appear to be tuned so that the cells can use either type of transition. The design principle identified here serves as the basis for the analysis and control of cellular collective decision making.</p>