Lattice ultrasensitivity produces large gain inE. colichemosensing

Abstract

AbstractE. coliuse a regular lattice of receptors and attached kinases to detect and amplify faint chemical signals. Kinase output is characterized by precise adaptation to a wide range of background ligand levels and large gain in response to small relative changes in ligand concentration. These characteristics are well described by models which achieve their gain through equilibrium cooperativity. But these models are challenged by two experimental results. First, neither adaptation nor large gain are present in receptor binding assays. Second, in cells lacking adaptation machinery, fluctuations can sometimes be enormous, with essentially all kinases transitioning together. Here we introduce a far-from equilibrium model in which receptors gate the spread of activity between neighboring kinases. This model achieves large gain through a mechanism we term lattice ultrasensitivity (LU). In our LU model, kinase and receptor states are separate degrees of freedom, and kinase kinetics are dominated by chemical rates far-from-equilibrium rather than by equilibrium allostery. The model recapitulates the successes of past models, but also matches the challenging experimental findings. Importantly, unlike past lattice critical models, our LU model does not require parameters to be fine tuned for function.