title: Communication shapes sensory response in multicellular networks.
abstract: Collective sensing by interacting cells is observed in a variety of biological systems, and yet, a quantitative understanding of how sensory information is collectively encoded is lacking. Here, we investigate the ATP-induced calcium dynamics of monolayers of fibroblast cells that communicate via gap junctions. Combining experiments and stochastic modeling, we find that increasing the ATP stimulus increases the propensity for calcium oscillations, despite large cell-to-cell variability. The model further predicts that the oscillation propensity increases with not only the stimulus, but also the cell density due to increased communication. Experiments confirm this prediction, showing that cell density modulates the collective sensory response. We further implicate cell-cell communication by coculturing the fibroblasts with cancer cells, which we show act as "defects" in the communication network, thereby reducing the oscillation propensity. These results suggest that multicellular networks sit at a point in parameter space where cell-cell communication has a significant effect on the sensory response, allowing cells to simultaneously respond to a sensory input and the presence of neighbors.
authors: Department of Physics, Oregon State University, Corvallis, OR 97331;
authors: Garrett D
authors: GD
authors: Potter
authors: Department of Physics and Astronomy, Purdue University, West Lafayette, IN 47907.
authors: Tommy A
authors: TA
authors: Byrd
authors: Department of Physics and Astronomy, Purdue University, West Lafayette, IN 47907 amugler@purdue.edu sunb@physics.oregonstate.edu.
authors: Andrew
authors: A
authors: Mugler
authors: Department of Physics, Oregon State University, Corvallis, OR 97331; amugler@purdue.edu sunb@physics.oregonstate.edu.
authors: Bo
authors: B
authors: Sun
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics; D002450:Cell Communication / Q000235:genetics*; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism; D017629:Gap Junctions / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D046210:Microfluidic Analytical Techniques; D041681:NIH 3T3 Cells
chemical_list: D000255:Adenosine Triphosphate; D002118:Calcium
keywords: calcium oscillations; cellular sensing; cell–cell communication; collective behavior; gap junctions