Abstract
Cells use surface receptors to estimate concentrations of external ligands. Limits on the accuracy of such estimations have been well studied for pairs of ligand and receptor species. However, the environment typically contains many ligands, which can bind to the same receptors with different affinities, resulting in cross-talk. In traditional rate models, such cross-talk prevents accurate inference of concentrations of individual ligands. In contrast, here we show that knowing the precise timing sequence of stochastic binding and unbinding events allows one receptor to provide information about multiple ligands simultaneously and with a high accuracy. We show that such high-accuracy estimation of multiple concentrations can be realized with simple structural modifications of the familiar kinetic proofreading biochemical network diagram. We give two specific examples of such modifications. We argue that structural and functional features of real cellular biochemical sensory networks in immune cells, such as feedforward and feedback loops or ligand antagonism, sometimes can be understood as solutions to the accurate multi-ligand estimation problem.
Highlights
Cells obtain information about their environment by capturing ligand molecules with receptors on their surface and estimating the ligand concentration from the receptor activity
Can cells estimate concentrations of more ligands than they have receptor types? In this paper, we show that, surprisingly, the answer is “yes”, and the estimation can be implemented with simple biochemical components already present in many cells
Simple biochemical networks allow accurate sensing of multiple ligands with a single receptor on the accuracy of such estimation have been a subject of interest since the seminal work of Berg and Purcell [1], with several substantial extensions found recently [2,3,4,5,6,7,8]
Summary
Cells obtain information about their environment by capturing ligand molecules with receptors on their surface and estimating the ligand concentration from the receptor activity. Simple biochemical networks allow accurate sensing of multiple ligands with a single receptor on the accuracy of such estimation have been a subject of interest since the seminal work of Berg and Purcell [1], with several substantial extensions found recently [2,3,4,5,6,7,8] Most of these assume one ligand species coupled to one receptor species, and the actual detection in most of these models is rather simple, involving counting the number or the duration of binding / unbinding events over a specific period of time. Real cellular sensory systems are incredibly complex, involving many dozens of identified biochemical species downstream of a typical receptor [9] Many of such signaling motifs are probably related to solving the cross-talk problem [10, 11], and are a topic of active research
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