Large number of receptors may reduce cellular response time variation

TL;DR

This paper proposes that having many cell receptors reduces activation time variability through competition, enabling synchronized and specific cellular responses without compromising ligand discrimination.

Contribution

It introduces a model showing how large receptor numbers decrease response time variability and predicts receptor counts that balance speed and specificity, aligning with experimental data.

Findings

Receptor competition reduces activation time variability.

Predicted receptor numbers match experimental observations.

Large receptor numbers do not impair ligand specificity.

Abstract

Cells often have tens of thousands of receptors, even though only a few activated receptors can trigger full cellular responses. Reasons for the overabundance of receptors remain unclear. We suggest that, in certain conditions, the large number of receptors results in a competition among receptors to be the first to activate the cell. The competition decreases the variability of the time to cellular activation, and hence results in a more synchronous activation of cells. We argue that, in simple models, this variability reduction does not necessarily interfere with the receptor specificity to ligands achieved by the kinetic proofreading mechanism. Thus cells can be activated accurately in time and specifically to certain signals. We predict the minimum number of receptors needed to reduce the coefficient of variation for the time to activation following binding of a specific ligand. Further, we predict the maximum number of receptors so that the kinetic proofreading mechanism still can improve the specificity of the activation. These predictions fall in line with experimentally reported receptor numbers for multiple systems.