Chemotaxis in Escherichia coli: A Molecular Model for Robust Precise Adaptation

Abstract

The chemotaxis system in the bacterium Escherichia coli is remarkably sensitive to small relative changes in the concentrations of multiple chemical signals over a broad range of ambient concentrations. Interactions among receptors are crucial to this sensitivity as is precise adaptation, the return of chemoreceptor activity to prestimulus levels in a constant chemoeffector environment. Precise adaptation relies on methylation and demethylation of chemoreceptors by the enzymes CheR and CheB, respectively. Experiments indicate that when transiently bound to one receptor, these enzymes act on small assistance neighborhoods (AN) of five to seven receptor homodimers. In this paper, we model a strongly coupled complex of receptors including dynamic CheR and CheB acting on ANs. The model yields sensitive response and precise adaptation over several orders of magnitude of attractant concentrations and accounts for different responses to aspartate and serine. Within the model, we explore how the precision of adaptation is limited by small AN size as well as by CheR and CheB kinetics (including dwell times, saturation, and kinetic differences among modification sites) and how these kinetics contribute to noise in complex activity. The robustness of our dynamic model for precise adaptation is demonstrated by randomly varying biochemical parameters. Bacteria swim in relatively straight lines and change directions through tumbling. In the process of chemotaxis, a network of receptors and other proteins controls the tumbling frequency to direct an otherwise random walk toward nutrients and away from repellents. Receptor clustering and adaptation to persistent stimuli through covalent modification allow chemotaxis to be sensitive over a large range of ambient concentrations. The individual components of the chemotaxis network are well characterized, and signaling measurements by fluorescence microscopy quantify the network's response, making the system well suited for modeling and analysis. In this paper, we expand upon a previous model based on experiments indicating that the covalent modifications required for adaptation occur through the action of enzymes on groups of neighboring receptors, referred to as assistance neighborhoods. Simulations show that our proposed molecular model of a strongly coupled complex of receptors produces accurate responses to different stimuli and is robust to parameter variation. Within this model, the correct adaptation response is limited by small assistance-neighborhood size as well as enzyme kinetics. We also explore how these kinetics contribute to noise in the chemotactic response.