Complexes of chemoreceptors in the bacterial cytoplasmic membrane allow for the sensing of ligands with remarkable sensitivity. Despite the excellent characterization of the chemotaxis signaling network, very little is known about what controls receptor complex size. Here we use in vitro signaling data to model the distribution of complex sizes. In particular, we model Tar receptors in membranes as an ensemble of different sized oligomer complexes, i.e., receptor dimers, dimers of dimers, and trimers of dimers, where the relative free energies, including receptor modification, ligand binding, and interaction with the kinase CheA determine the size distribution. Our model compares favorably with a variety of signaling data, including dose-response curves of receptor activity and the dependence of activity on receptor density in the membrane. We propose that the kinetics of complex assembly can be measured in vitro from the temporal response to a perturbation of the complex free energies, e.g., by addition of ligand.
Chemotaxis allows bacteria to sense and swim toward nutrients and away from toxins. The remarkable sensing properties of the chemotaxis network, such as high sensitivity to small changes in the chemical environment, are thought to originate from receptor complexes in the membrane, which act as antennas to magnify weak signals. To adapt to persistent stimulation, receptors are covalently modified. While the individual protein components of the chemotaxis network are well characterized, making the system well suited for quantitative and computational analysis, direct experimental visualization of receptors and receptor complexes is difficult within the current limits of fluorescence and electron microscopy. To address questions such as how large are complexes and why do they assemble, we analyze in vitro signaling data using a previously developed model of signaling by receptor complexes. Based on the data, we propose a statistical physics model for the distribution of complex sizes in the membrane. Within this model, complex size depends on the receptor free energy with contributions from receptor modification level, ligand binding, receptor–receptor coupling, and binding to accessory proteins. Our model results compare favorably with a variety of different signaling data, and suggest new experiments to measure the kinetics of assembly of receptor complexes.