Chemotactic bacteria such as Escherichia coli can detect and respond to extremely low concentrations of attractants, concentrations of less than 5 nM in the case of aspartate. They also sense gradients of attractants extending over five orders of magnitude in concentration (up to 1 mM aspartate). Here we consider the possibility that this combination of sensitivity and range of response depends on the clustering of chemotactic receptors on the surface of the bacterium. We examine what will happen if ligand binding changes the activity of a receptor, propagating this change in activity to neighbouring receptors in a cluster. Calculations based on these assumptions show that sensitivity to extracellular ligands increases with the extent of spread of activity through an array of receptors, but that the range of concentrations over which the array works is severely diminished. However, a combination of low threshold of response and wide dynamic range can be attained if the cell has both clusters and single receptors on its surface, particularly if the extent of activity spread can adapt to external conditions. A mechanism of this kind can account quantitatively for the sensitivity and response range of E. coli to aspartate.

Coliform bacteria detect chemical attractants by means of a membrane-associated cluster of receptors and signalling molecules. We have used recently determined molecular structures, in conjunction with plastic models generated by three-dimensional printer technology, to predict how the proteins of the complex are arranged in relation to the plasma membrane. The proposed structure is a regular two-dimensional lattice in which the cytoplasmic ends of chemotactic-receptor dimers are inserted into a hexagonal array of CheA and CheW molecules. This structure creates separate compartments for adaptation and downstream signalling, and indicates a possible basis for the spread of activity within the cluster.

Our results display the potential use of computer-based bacteria as experimental objects for exploring subtleties of chemotactic behavior.

Cells in a cloned population of coliform bacteria exhibit a wide range of swimming behaviors--a form of non-genetic individuality. We used computer models to examine the proposition that these variations are due to differences in the number of chemotaxis signaling molecules from one cell to the next. Simulations were run in which the concentrations of seven gene products in the chemotaxis pathway were changed either deterministically or stochastically, with the changes derived from independent normal distributions. Computer models with two adaptation mechanisms were compared with experimental results from observations on individuals drawn from genetically identical populations. The range of swimming behavior predicted for cells with a standard deviation of protein copy number per cell of 10% of the mean was found to match closely the experimental range of the wild-type population. We also make predictions for the swimming behaviors of mutant strains lacking the adaptational mechanism that can be tested experimentally.

Adaptation of the attractant response in Escherichia coli is attributable to the methylation of its transmembrane chemotactic receptors by the methyltransferase CheR. This protein contains two binding domains, one for the sites of methylation themselves and the other for a flexible tether at the C terminus of the receptor. We have explored the theoretical consequences of this binding geometry for a CheR molecule associated with a cluster of chemotactic receptors. Calculations show that the CheR molecule will bind with high net affinity to the receptor lattice, having a high probability of being attached by one or both of its domains at any instant of time. Because of the relatively low affinity of its individual domains and the close proximity of neighboring receptors, it is likely that when one domain unbinds it will reattach to the array before the other domain unbinds. Stochastic simulations show that the enzyme will move through the receptor cluster in a hand-over-hand fashion, like a gibbon swinging through the branches of a tree. We explore the possible consequences of this motion, which we term "molecular brachiation", for chemotactic adaptation and suggest that a similar mechanism may be operative in other large assemblies of protein molecules.