Physical limit to concentration sensing amid spurious ligands

TL;DR

This paper derives the fundamental physical limit on how accurately cells can sense ligand concentrations when spurious ligands interfere, revealing a key transition point and proposing receptor cascade strategies to approach this limit.

Contribution

It analytically establishes the physical limit to concentration sensing accuracy amid interfering ligands and introduces receptor cascade schemes to approach this bound.

Findings

Identifies a scaling transition at twice the mean bound time of correct ligands.

Derives an analytical expression for the sensing limit amid spurious ligands.

Proposes receptor cascade strategies to approach the physical sensing bound.

Abstract

To adapt their behaviour 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 proof-reading schemes.