A tunable population timer in multicellular consortia

Abstract

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: sets of genes connected to achieve specific tasks. However, such systems are difficult to implement in single cells due to saturation in molecular components and stochasticity in the limited intracellular space. Multicellular implementations, on the other hand, outsource some of the components of information-processing circuits to the extracellular space, and thereby might escape those constraints. Here we develop a theoretical framework, based on a trilinear coordinate representation, to study the collective behavior of a cellular population 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 cell types enables the robust implementation of a multicellular timer. Our analysis also shows the circuit to be easily tunable by varying the cellular composition of the consortium.