Receptor crosstalk improves concentration sensing of multiple ligands

TL;DR

This paper shows that receptor crosstalk, often seen as a flaw, can actually enhance the accuracy of cells in detecting multiple ligand concentrations by utilizing information from non-cognate ligand binding events.

Contribution

It quantifies the optimal sensing precision with receptor crosstalk and proposes a proofreading scheme to approach these bounds, explaining the prevalence of crosstalk in biological systems.

Findings

Crosstalk can improve sensing precision and discrimination.

Short non-cognate binding events contain useful information.

A proofreading scheme approaches optimal sensing bounds.

Abstract

Cells need to reliably sense external ligand concentrations to achieve various biological functions such as chemotaxis or signaling. The molecular recognition of ligands by surface receptors is degenerate in many systems leading to crosstalk between different receptors. Crosstalk is often thought of as a deviation from optimal specific recognition, as the binding of non-cognate ligands can interfere with the detection of the receptor's cognate ligand, possibly leading to a false triggering of a downstream signaling pathway. Here we quantify the optimal precision of sensing the concentrations of multiple ligands by a collection of promiscuous receptors. We demonstrate that crosstalk can improve precision in concentration sensing and discrimination tasks. To achieve superior precision, the additional information about ligand concentrations contained in short binding events of the non-cognate ligand should be exploited. We present a proofreading scheme to realize an approximate estimation of multiple ligand concentrations that reaches a precision close to the derived optimal bounds. Our results help rationalize the observed ubiquity of receptor crosstalk in molecular sensing.