Flagellar dynamics reveal fluctuations and kinetic limit in the Escherichia coli chemotaxis network

Abstract

Biochemical signaling networks allow living cells to adapt to a changing environment, but these networks must cope with unavoidable number fluctuations ("noise") in their molecular constituents. Escherichia coli chemotaxis, by which bacteria modulate their random run/tumble swimming pattern to navigate their environment, is a paradigm for the role of noise in cell signaling. The key signaling protein, CheY, when activated by (reversible) phosphorylation, causes a switch in the rotational direction of the flagellar motors propelling the cell, leading to tumbling. CheY-P concentration,[CheY-P], is thus a measure of the chemotaxis network's output, and temporal fluctuations in [CheY-P] provide a proxy for network noise. Here we quantify the fluctuations in [CheY-P] from the switching dynamics of individual flagella, observed using time-resolved fluorescence microscopy of optically trapped E. coli cells. This approach reveals [CheY-P] fluctuations at steady state, which may play a critical role in driving flagellar switching and cell tumbling. A stochastic theoretical model, inspired by work on gene expression noise, points to CheY activation occurring in bursts, driving the [CheY-P] fluctuations. When the network is stimulated chemically to higher activity, we observe a dramatic decrease in [CheY-P] fluctuations. Our stochastic model shows that an intrinsic kinetic ceiling on network activity places an upper limit on [CheY-P], which when encountered suppresses its fluctuations. This limit may also prevent cells from tumbling unproductively in steep gradients.