Molecular-level tuning of cellular autonomy controls the collective behaviors of cell populations
A rigorous understanding of how multicellular behaviors arise from the actions of single cells requires quantitative frameworks that bridge the gap between genetic circuits, the arrangement of cells in space, and population-level behaviors. Here, we provide such a framework for a ubiquitous class of multicellular systems - namely, "secrete-and-sense cells" that communicate by secreting and sensing a signaling molecule. By using formal, mathematical arguments and introducing the concept of a phenotype diagram, we show how these cells tune their degrees of autonomous and collective behavior to realize distinct single-cell and population-level phenotypes; these phenomena have biological analogs, such as quorum sensing or paracrine signaling. We also define the "entropy of population," a measurement of the number of arrangements that a population of cells can assume, and demonstrate how a decrease in the entropy of population accompanies the formation of ordered spatial patterns. Our conceptual framework ties together diverse systems, including tissues and microbes, with common principles.
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