Sensitivity, feedback and fluctuations in bacterial chemotaxis

Thomas Shimizu (Harvard University)

Abstract

Chemotaxis in E. coli has played a paradigmatic role in the transformation of cell signaling research in to a quantitative discipline. Three important quantitative features of this sensory system have been highlighted, namely, exact adaptation, high sensitivity and wide dynamic range. All three are required for the problem every bacterium would like to solve: how to navigate up shallow gradients a very long way. Exact adaptation can be explained elegantly by the simple mechanism of activity-dependent feedback in the receptor modification system, whereas high sensitivity and wide dynamic range were shown to be attainable by simple physical interactions between clustered receptors. Here we utilize in vivo FRET measurements of pathway activity to study how these mechanisms combine in the physiology of living cells. We find that a simplified view of receptor interactions analogous to classical MWC-type models of allostery [4] suffices to describe the dose-response characteristics of adaptation-deficient cells with fixed modification states. We extend this model to analyze the behavior of adapting cells where receptor modification levels are dynamically tuned by adaptive feedback. Because of the intrinsic stochasticity of chemical reactions, the modification levels of receptors fluctuate, resulting in a heterogeneous population at steady state. We study how different mechanisms of feedback affect these distributions, which, in turn, determine the sensitivity and cooperativity of receptor populations.

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