Balancing specificity, sensitivity and speed of ligand discrimination by zero-order ultraspecificity

TL;DR

This paper demonstrates that zero-order ultrasensitivity naturally enhances ligand discrimination by balancing specificity, sensitivity, and speed, providing insights into cellular decision-making processes.

Contribution

It reveals that zero-order ultrasensitivity underpins ultraspecificity in ligand discrimination, offering a new perspective on biochemical reaction nonlinearities.

Findings

Zero-order ultrasensitivity leads to ultraspecificity in ligand recognition.

The mechanism balances discrimination speed, sensitivity, and specificity.

A model for insensitivity to many non-target ligands is derived.

Abstract

Specific interactions between receptors and their target ligands in the presence of non-target ligands are crucial for biological processes such as T cell ligand discrimination. To discriminate between the target and non-target ligands, cells have to increase specificity by amplifying the small differences in affinity among ligands. In addition, sensitivity to ligand concentration and quick discrimination are also important to detect low amounts of target ligands and facilitate fast cellular decision making after ligand recognition. In this work, we find that ultraspecificity is naturally derived from a well-known mechanism for zero-order ultrasensitivity to concentration. We also show that this mechanism can produce an optimal balance of specificity, sensitivity, and quick discrimination. Furthermore, we show that a model for insensitivity to large number of non-terget ligands can be naturally derived from the ultraspecificity model. Zero-order ultraspecificity may provide alternative way to understand ligand discrimination from the viewpoint of the nonlinear properties of biochemical reactions.