Protein gradients and clustering dynamics in bacterial chemotaxis

Karen Lipkow, University of Cambridge, Cambridge.

The chemotaxis pathway of Escherichia coli, which enables the bacterium to swim to the most beneficial environment, is the best-understood to date. Signals from the environment are detected by transmembrane receptor-kinase complexes, which are mostly clustered at the cell pole, and then transmitted to the randomly positioned flagellar motors by diffusion of the phosphorylated CheYp protein. A component of the pathway which promotes dephosphorylation of CheYp, the protein CheZ, has been shown by fluorescent methods to be distributed between the cytoplasm and the receptor cluster.

With the aid of a computer program that can simulate the movement and interaction of a large number of individual molecules in a structured environment (Andrews & Bray, Phys. Biol., 2004), we constructed a three-dimensional model of an E. coli cell. We examined the generation and diffusion of CheYp through the cell under control conditions and in response to attractant and repellent stimuli. The results agree well with experimental observations but allow an analysis at much higher detail, such as the calculation of diffusion traces and lifetimes of individual molecules. Exploring the effects of cellular architecture, macromolecular crowding and positioning of the CheZ phosphatase, we identified conditions for the formation of gradients of phosphorylated CheY (Lipkow et al., J. Bacteriol., 2005).

Supported by analytical methods and simulations, we demonstrate that intracellular gradients can have an unexpectedly complicated form. This will occur, for example, if one of the phospho-states binds to a large or immobile structure and needs to be taken into account when measuring gradients experimentally, for example via FRET probes. We present a model in which CheZ dynamically changes location and self-organises into oligomeric clusters of higher activity at the pole depending on stimulus level. Our simulations suggest that the changing location of CheZ will sharpen responses of the cell, make adaptation more precise, and increase the range of detectable ligand concentrations. They introduce an unprecedented level of sophistication into what is usually considered a simple signalling pathway.


Vincent Moulton
© 2005, CBL
Computational Biology Laboratory,
School of Computing Sciences,
University of East Anglia,
Norwich, NR4 7TJ, UK.