Helping cells jump to conclusions.

Abstract

Many cellular processes rely on the ability of cells to sense and respond to chemical information in their immediate surroundings. Cells can achieve this by binding chemical signals (ligand) to specific receptor proteins, that convert the chemical information into intracellular signals to which the cells can respond. Furthermore, different concentrations of ligand may be distinguished by the fraction of bound to unbound receptor. Although this is generally only possible for concentrations that do not saturate the receptors, it was recently shown that cells' ability to distinguish between ligand concentrations could in theory be expanded into the saturating range, by the utilization of pre-equilibrium information resulting from the ligand--receptor binding kinetics. This mechanism was termed pre-equilibrium sensing and signaling (PrESS). Here, the possibility to biologically implement this idea as a simple, controllable genetic circuit is investigated. Via computational modeling and experiments it is shown that repression-based sensing, aided by slow influx of ligand, generates pre-equilibrium dynamics that may enable cells to distinguish between different saturating concentrations of ligand. However, these dynamics differ from those originally described for PrESS, making the system less general. Potential modifications to generate more PrESS-like dynamics are therefore also discussed.