A tunable population timer in multicellular consortia

Abstract

Summary Processing time-dependent information requires cells to quantify the duration of past regulatory events and program the time span of future signals. At the single-cell level, timer mechanisms can be implemented with genetic circuits. However, such systems are difficult to implement in single cells due to saturation in molecular components and stochasticity in the limited intracellular space. In contrast, multicellular implementations outsource some of the components of information-processing circuits to the extracellular space, potentially escaping these constraints. Here, we develop a theoretical framework, based on trilinear coordinate representation, to study the collective behavior of populations composed of three cell types under stationary conditions. This framework reveals that distributing different processes (in our case the production, detection and degradation of a time-encoding signal) across distinct strains enables the implementation of a multicellular timer. Our analysis also shows that the circuit can be easily tunable by varying the cellular composition of the consortium.