Communication shapes sensory response in multicellular networks

TL;DR

This study combines experiments and stochastic modeling to show how cell communication influences collective sensory responses in fibroblast monolayers, revealing that cell density and communication defects modulate calcium oscillations.

Contribution

It provides a quantitative analysis of how cell-cell communication affects collective sensory encoding, integrating experimental data with stochastic modeling.

Findings

Increased ATP stimulus raises calcium oscillation propensity.

Higher cell density enhances collective response via communication.

Cancer cell coculture reduces oscillation propensity by disrupting communication.

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 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.