Bacterial chemotaxis: sensory adaptation, noise filtering, and information transmission

Abstract

Chemotaxis is a fundamental cellular process by which cells sense and navigate in their environment. The molecular signalling pathway in the bacterium Escherichia coli is experimentally well-characterised and, hence, ideal for quantitative analysis and modelling. Chemoreceptors sense gradients of a multitude of substances and regulate an intracellular signalling pathway, which modulates the swimming behaviour. We studied the chemotaxis pathway in E. coli (i) to quantitatively understand molecular interactions in the signalling network, (ii) to gain a systems view of the workings of the pathway, including the effects of noise generated by biomolecular reactions during signalling, and (iii) to understand general design principles relevant for many sensory systems. Specifically, we investigated the adaptation dynamics due to covalent chemoreceptor modification, which includes numerous layers of feedback regulation. In collaboration with an experimental group, we undertook quantitative experiments using wild-type cells and mutants for proteins involved in adaptation using in vivo fluorescence resonance transfer (FRET). We developed a dynamical model for chemotactic signalling based on cooperative chemoreceptors and adaptation of the sensory response. This model quantitatively explains an interesting asymmetry of the response to favourable and unfavourable stimuli observed in the experiments. In a whole-pathway description, we further studied the response to controlled concentration stimuli, as well as how fluctuations from the environment and due to intracellular signalling affect the detection of input signals. Finally, the chemotaxis pathway is characterised by high sensitivity, a wide dynamic range and the need for information transmission, properties shared with many other sensory systems. Based on FRET data, we investigated the emergence, limits and biological significance of Weber’s law which predicts that the system detects stimuli relative to the background stimulus. Furthermore, we studied the information transmission from input concentrations into intracellular signals. We connect Weber’s law, as well as information transmission, to swimming bacteria and predict typically encountered chemical inputs.