Modeling Cell-to-Cell Communication Networks Using Response-Time Distributions

Kevin Thurley, Lani F. Wu, Steven J. Altschuler
2018 Cell Systems  
Cell-to-cell communication networks have critical roles in coordinating diverse organismal processes, such as tissue development or immune cell response. However, compared with intracellular signal transduction networks, the function and engineering principles of cell-to-cell communication networks are far less understood. Major complications include: cells are themselves regulated by complex intracellular signaling networks; individual cells are heterogeneous; and output of any one cell can
more » ... ursively become an additional input signal to other cells. Here, we make use of a framework that treats intracellular signal transduction networks as "black boxes" with characterized input-to-output response relationships. We study simple cell-to-cell communication circuit motifs and find conditions that generate bimodal responses in time, as well as mechanisms for independently controlling synchronization and delay of cell-population responses. We apply our modeling approach to explain otherwise puzzling data on cytokine secretion onset times in T cells. Our approach can be used to predict communication network structure using experimentally accessible input-to-output measurements and without detailed knowledge of intermediate steps. In Brief This is an open access article under the CC BY license Interacting cellular communities have critical roles in biological functions such as tissue development or immune responses. Cell-to-cell communication networks comprise both intra-and intercellular processes, making detailed mathematical models intractable. Here, we develop a scalable framework for modeling extra-cellular communication networks that treats intracellular signal transduction networks as "black boxes" with characterized input-to-output response relationships. We discover that a range of dynamic cell-population behaviors, including cellular synchronization, delays, and bimodal responses, can emerge from simple cell-to-cell communication networks. Thurley et al.
doi:10.1016/j.cels.2018.01.016 pmid:29525203 pmcid:PMC5913757 fatcat:j7vaa2urnvf4rkfmi4g57tolnq