Collective sensing by many interacting cells is observed in a variety of biological systems, and yet a quantitative understanding of how sensory information is encoded by many cells is still lacking. In this study, we characterize the calcium dynamics of cocultured monolayers of fibroblast cells and breast cancer cells in response to external ATP stimuli. We find that gap junctional communication is suppressed by the presence of cancer cells, similar in effect to reducing cell density. The ATP-induced calcium dynamics of nearest neighbor cells are correlated, and the cross-correlation functions depend on both ATP concentration and the architecture of the multicellular network. Combining experiments and stochastic modeling, we find that networks with sparse or defective connectivity have a reduced propensity for calcium oscillations and exhibit a broader distribution of oscillation frequencies. We find that cell-to-cell variability makes the conventional model of frequency encoding ineffective for a large population of communicating cells. Instead, our results suggest that multicellular networks URLanized near a dynamical critical point which allows cell-to-cell communications to significantly modulate the collective cellular dynamics .
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 not only with the stimulus, but also with 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 to the presence of neighbors .
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encoded by many cells is still lacking. In this study, we characterize the
collectively encoded is lacking. Here we investigate the ATP-induced
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cocultured
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and breast cancer cells in response to external ATP stimuli. We find that gap junctional communication is suppressed by the presence of cancer cells, similar in effect to reducing cell density. The ATP-induced calcium dynamics of nearest neighbor cells are correlated, and the cross-correlation functions depend on both ATP concentration and the architecture of the multicellular network.
that communicate via gap junctions.
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networks with sparse or defective connectivity have a reduced
increasing the ATP stimulus increases the
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and exhibit a broader distribution of oscillation frequencies. We find that
despite large
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variability makes the conventional model of frequency encoding ineffective for a large population of communicating cells. Instead, our
variability. The model further predicts that the oscillation propensity increases not only with the stimulus, but also with 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
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URLanized near a dynamical critical point which allows cell-to-cell communications to significantly modulate the collective cellular dynamics
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 to the presence of neighbors