Abstract
Cell-to-cell communication networks have critical roles in diverse organismal processes, such as coordinating tissue development or immune cell response. However, compared to intracellular signal transduction networks, the function and engineering principles of cell-to-cell communication networks are far less understood. Here, we study cell-to-cell communication networks using a framework that models the input-to-output relationship of intracellular signal transduction networks with a single function—the response-time distribution. We identified a prototypic response-time distribution—the gamma distribution—arising in both experimental data sets and mathematical models of signal-transduction pathways. We discover that a range of cellular behaviors, including cellular synchronization, delays and bimodal responses, can emerge from simple cell-to-cell communication networks. We apply our modeling approach to provide a plausible explanation for otherwise puzzling data on cytokine secretion onset times in a T cell population. Our approach can be used to predict communication network structure using experimentally accessible input-to-output measurements and without detailed knowledge of intermediate steps.