Signal duration and the time scale dependence of signal integration in biochemical pathways

TL;DR

This paper analyzes how biochemical pathways process signals of different durations, revealing design principles that explain the prevalence of multi-step regulation for controlling biological decisions across various contexts.

Contribution

It introduces a framework for understanding how simple biochemical motifs can differentially process signals based on their time scales using dynamic gain and power spectra analysis.

Findings

Identification of network topologies that enable frequency-dependent signal processing

Demonstration that multi-step regulation enhances control over signal duration

Proposal of design principles for signal duration control in biochemical systems

Abstract

Signal duration (e.g. the time scales over which an active signaling intermediate persists) is a key regulator of biological decisions in myriad contexts such as cell growth, proliferation, and developmental lineage commitments. Accompanying differences in signal duration are numerous downstream biological processes that require multiple steps of biochemical regulation. Here, we present an analysis that investigates how simple biochemical motifs that involve multiple stages of regulation can be constructed to differentially process signals that persist at different time scales. We compute the dynamic gain within these networks and resulting power spectra to better understand how biochemical networks can integrate signals at different time scales. We identify topological features of these networks that allow for different frequency dependent signal processing properties. Our studies suggest design principles for why signal duration in connection with multiple steps of downstream regulation is a ubiquitous control motif in biochemical systems.