AbstractInteractions between cells drive biological processes across all of life, from microbes in the environment to cells in multicellular organisms. Interactions often arise in spatially structured settings, where cells mostly interact with their neighbors. A central question is how the properties of biological systems emerge from local interactions. This question is very relevant in the context of microbial communities, such as biofilms, where cells live close by in space and are connected via a dense network of biochemical interactions. To understand and control the functioning of these communities, it is essential to uncover how community-level properties, such as the community composition, spatial arrangement, and growth rate, arise from these interactions. Here, we develop a mathematical framework that can predict community-level properties from the molecular mechanisms underlying the cell-cell interactions for systems consisting of two cell types. Our predictions match quantitative measurements from an experimental cross-feeding community. For these cross-feeding communities, the community growth rate is reduced when cells interact only with few neighbors; as a result, some communities can co-exist in a well-mixed system, but not in a spatial one. In general, our framework shows that key molecular parameters underlying the cell-cell interactions (e.g. the uptake and leakage rates of molecules) determine community level properties. Our framework can be extended to a variety of systems of two interacting cell types, within and beyond the microbial world, and contributes to our understanding of how biological functions arise from interactions between single cells.
Molecular mechanisms of cancer cell-cell interactions
