Signaling in microbial communities with open boundaries

Microbial communities such as swarms or biofilms often form at the interfaces of solid substrates and open fluid flows. At the same time, in laboratory environments these communities are commonly studied using microfluidic devices with media flows and open boundaries. Extracellular signaling within these communities is therefore subject to different constraints than signaling within classic, closed-boundary systems such as developing embryos or tissues, yet is understudied by compar-ison. Here, we use mathematical modeling to show how advective-diffusive boundary flows and population geometry impact cell-cell signaling in monolayer microbial communities. We reveal conditions where the intercellular signaling lengthscale depends solely on the population geometry and not on diffusion or degradation, as commonly expected. We further demonstrate that diffusive coupling with the boundary flow can produce signal gradients within an isogenic population, even when there is no flow within the population. We use our theory to provide new insights into the signaling mechanisms of published experimental results, and we make several experimentally verifiable predictions. Our research highlights the importance of carefully evalu-ating boundary dynamics and environmental geometry when modeling microbial cell-cell signaling and informs the study of cell behaviors in both natural and synthetic systems.SIGNIFICANCE Microbial communities in natural environments and microfluidic devices are often exposed to open boundaries and flows, but models used to characterize diffusive signaling in such systems often ignore how device geometry, boundary conditions, and media flow influence signaling behavior. We demonstrate how the effective signaling capacity of these communities can be shaped by population geometry and advective-diffusive boundary flow in quasi-2D environments. Our approach provides a general framework to understand and control advection-reaction-diffusion systems-and their interactions with cellular signaling networks-in both natural and synthetic environments.