Fundamental limits to collective concentration sensing in cell populations

TL;DR

This paper derives the fundamental physical limits of concentration sensing accuracy in cell populations that communicate via juxtacrine or autocrine signaling, revealing conditions where autocrine signaling outperforms juxtacrine.

Contribution

It provides a theoretical framework quantifying the limits of collective sensing in cells and identifies optimal cell spacing strategies for different signaling modes.

Findings

Autocrine signaling can enable more precise sensing than juxtacrine for large populations.

Optimal cell spacing balances communication strength and signal correlation.

Theoretical limits match observed data across various cell types.

Abstract

The precision of concentration sensing is improved when cells communicate. Here we derive the physical limits to concentration sensing for cells that communicate over short distances by directly exchanging small molecules (juxtacrine signaling), or over longer distances by secreting and sensing a diffusive messenger molecule (autocrine signaling). In the latter case, we find that the optimal cell spacing can be large, due to a tradeoff between maintaining communication strength and reducing signal cross-correlations. This leads to the surprising result that autocrine signaling allows more precise sensing than juxtacrine signaling for sufficiently large populations. We compare our results to data from a wide variety of communicating cell types.