title: A spatially extended stochastic model of the bacterial chemotaxis signalling pathway.
abstract: We have combined two distinct but related stochastic approaches to model the Escherichia coli chemotaxis pathway. Reactions involving cytosolic components of the pathway were assumed to obey the laws of conventional stochastic chemical kinetics, while the clustered membrane receptors were represented in two-dimensional arrays similar to the Ising model. Receptors were assumed to flip between an active and an inactive state with probabilities dependent upon three energy inputs: ligand binding, methylation level due to adaptation, and the activity of neighbouring receptors. Examination of models with different lattice size and geometry showed that the sensitivity to stimuli increases with lattice size and the nearest-neighbour coupling strength up to a critical point, but this amplification was also accompanied by a proportional increase in steady-state noise. Multiple methylation of receptors resulted in diminished signal-to-noise ratio, but showed improved stability to variation in the coupling strength and increased gain. Under the best conditions the simulated output of a coupled lattice of receptors closely matched the time-course and amplitude found experimentally in living bacteria. The model also has some of the properties of a cellular automaton and shows an unexpected emergence of spatial patterns of methylation within the receptor lattice.
authors.affiliation: Department of Zoology, University of Cambridge, UK. tom@sfc.keio.ac.jp
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Shimizu
authors.forename: Sergej V
authors.initials: SV
authors.lastname: Aksenov
authors.forename: Dennis
authors.initials: D
authors.lastname: Bray
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology*; D003198:Computer Simulation; D004926:Escherichia coli / Q000502:physiology*; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D000072236:Methyl-Accepting Chemotaxis Proteins; D008958:Models, Molecular; D011487:Protein Conformation; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D013269:Stochastic Processes; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface