Physical Limit to Concentration Sensing Amid Spurious Ligands

To adapt their behavior in changing environments, cells sense concentrations by binding external ligands to their receptors. However, incorrect ligands may bind nonspecifically to receptors, and when their concentration is large, this binding activity may interfere with the sensing of the ligand of interest. Here, I derive analytically the physical limit to the accuracy of concentration sensing amid a large number of interfering ligands. A scaling transition is found when the mean bound time of correct ligands is twice that of incorrect ligands. I discuss how the physical bound can be approached by a cascade of receptor states generalizing kinetic proofreading schemes.