Near-critical tuning of cooperativity revealed by spontaneous switching in a protein signalling array

Dynamic properties of allosteric complexes are crucial for signal processing by diverse cellular networks. However, direct observations of switches between distinct signaling states have been limited to compact molecular assemblies. Here, we report in vivo FRET measurements of spontaneous discrete-level fluctuations in the activity of the Escherichia coli chemosensory array — an extensive membrane-associated assembly comprising thousands of molecules. Finite-size scaling analysis of the temporal statistics by a two-dimensional conformational spread model revealed nearest-neighbor coupling strengths within 3% of the Ising transition point, indicating that chemosensory arrays are poised at criticality. Our analysis yields estimates for the intrinsic timescale of conformational changes (12-35 ms) of allosteric units, and identifies near-critical tuning as a design principle for balancing the inherent tradeoff between reponse amplitude and response speed in higher-order signaling assemblies. These results demonstrate the power of using fluctuation signatures of protein complexes to understand their function. One-setence summary In vivo measurements of protein signaling array fluctuations reveal an allosteric system poised at criticality.