Utilization of extracellular information before ligand-receptor binding reaches equilibrium expands and shifts the input dynamic range

Significance Many cell decisions depend on precise measurements of external ligands reversibly bound to receptors. Yeast cells orient in gradients of sex pheromone detecting differences in the amount of ligand-receptor complex. However, yeast can orient in gradients with nearly all receptors occupied. We describe a general systems-level mechanism, pre-equilibrium sensing and signaling (PRESS), which overcomes this saturation limit by shifting and expanding the input dynamic range to which cells can respond. PRESS requires that events downstream of the receptor be transient and faster than the time required for the receptor to reach equilibrium binding. Experiments and simulations show that PRESS operates in yeast and may help cells orient in gradients. Many ligand-receptor interactions are slow, suggesting that PRESS is widespread throughout eukaryotes.