Cooperative Model of Bacterial Sensing

Cooperative interactions among sensory receptors provide a general mechanism to increase the sensitivity of signal transduction. In particular, bacterial chemotaxis receptors interact cooperatively to produce an ultrasensitive response to chemoeffector concentrations. However, cooperativity between receptors in large macromolecular complexes is necessarily based on local interactions and consequently is fundamentally connected to slowing of receptor conformational dynamics, w...

We present a so-called adaptive Ising model (AIM) to provide a unifying explanation for sensitivity and perfect adaptation in bacterial chemotactic signalling, based on coupling among receptor dimers. In an AIM, an external field, representing ligand binding, is randomly applied to a fraction of spins, representing the states of the receptor dimers, and there is a delayed negative feedback from the spin value on the local field. This model is solved in an adiabatic approach. ...

Many eukaryotic cells are able to sense chemical gradients by directly measuring spatial concentration differences. The precision of such gradient sensing is limited by fluctuations in the binding of diffusing particles to specific receptors on the cell surface. Here, we explore the physical limits of the spatial sensing mechanism by modeling the chemotactic cell as an Ising spin chain subject to a spatially varying field. This allows us to derive the maximum likelihood estim...

Bacterial chemotaxis is controlled by the conformational changes of the receptors, in response to the change of the ambient chemical concentration. In a statistical mechanical approach, the signalling due to the conformational changes is a thermodynamic average quantity, dependent on the temperature and the total energy of the system, including both ligand-receptor interaction and receptor-receptor interaction. This physical theory suggests to biology a new understanding of c...

A stochastic version of the Barkai-Leibler model of chemotaxis receptors in {\it E. coli} is studied here to elucidate the effects of intrinsic network noise in their conformational dynamics. It was originally proposed to explain the robust and near-perfect adaptation of {\it E. coli} observed across a wide range of spatially uniform attractant/repellent (ligand) concentrations. A receptor is either active or inactive and can stochastically switch between the two states. Enzy...

In many sensory systems, transmembrane receptors are spatially organized in large clusters. Such arrangement may facilitate signal amplification and the integration of multiple stimuli. However, this organization likely also affects the kinetics of signaling since the cytoplasmic enzymes that modulate the activity of the receptors must localize to the cluster prior to receptor modification. Here we examine how these spatial considerations shape signaling dynamics at rest and ...

Sensory adaptation enables organisms to adjust their perception in a changing environment. A paradigm is bacterial chemotaxis, where the output activity of chemoreceptors is adapted to different baseline concentrations via receptor methylation. The range of internal receptor states limits the stimulus magnitude to which these systems can adapt. Here, we employ a highly idealized, Langevin-equation based model to study how the finite range of state variables affects the adapta...

We show how the competition between sensing and adaptation can result in a performance peak in E.coli chemotaxis using extensive numerical simulations in a detailed theoretical model. Receptor clustering amplifies the input signal coming from ligand binding which enhances chemotactic efficiency. But large clusters also induce large fluctuations in total activity since the number of clusters go down. The activity and hence the run-tumble motility now gets controlled by methyla...

We study methylation dynamics of the chemoreceptors as an {\sl E.coli} cell moves around in a spatially varying chemo-attractant environment. We consider attractant concentration with strong and weak spatial gradient. During the uphill and downhill motion of the cell along the gradient, we measure the temporal variation of average methylation level of the receptor clusters. Our numerical simulations show that the methylation dynamics depends sensitively on the size of the rec...

Receptors of bacterial chemotaxis form clusters at the cell poles, where clusters act as "antennas" to amplify small changes in ligand concentration. Interestingly, chemoreceptors cluster at multiple length scales. At the smallest scale, receptors form dimers, which assemble into stable timers of dimers. At a large scale, trimers form large polar clusters composed of thousands of receptors. Although much is known about the signaling properties emerging from receptor clusters,...