Accurate sensing of multiple ligands with a single receptor

Cells use surface receptors to estimate the concentration of external ligands. Limits on the accuracy of such estimations have been well studied for pairs of ligand and receptor species. However, the environment typically contains many ligands, which can bind to the same receptors with different affinities, resulting in cross-talk. In traditional rate models, such cross-talk prevents accurate inference of individual ligand concentrations. In contrast, here we show that knowing the precise timing sequence of stochastic binding and unbinding events allows one receptor to provide information about multiple ligands simultaneously and with a high accuracy. We argue that such high-accuracy estimation of multiple concentrations can be realized by the familiar kinetic proofreading mechanism.