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Decoupling between activation time and steady-state level in input-output responses.

Giorgio Ravanelli^1,2, Kee-Myoung Nam³, Jeremy Gunawardena³

¹CRG (Barcelona Collaboratorium for Modelling and Predictive Biology), C/ Dr Aiguader 88, 08003, Barcelona, Spain.

Biorxiv : the Preprint Server for Biology

|September 18, 2025

Summary

This summary is machine-generated.

Researchers explored output decoupling in biological systems, finding that input concentration can alter response levels without changing activation time. This phenomenon is explained by rate scale separation or incoherent regulation mechanisms.

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Area of Science:

Systems Biology
Biophysics
Molecular Biology

Background:

Biological processes involve molecular inputs binding to targets, triggering downstream responses.
Gene regulation by transcription factors (TFs) can exhibit output decoupling, where higher TF concentrations increase transcription without altering activation time.

Purpose of the Study:

Investigate mechanisms of output decoupling in Markov process models.
Identify conditions where steady-state readout levels change with input concentration, but activation time remains constant.

Main Methods:

Utilized analytical and numerical investigations of Markov process models.
Modeled readout molecule production downstream of ligand binding.

Main Results:

Identified two mechanisms for output decoupling: rate scale separation and incoherent regulation.
Rate scale separation involves input differentially regulating slow and fast system transitions.
Incoherent regulation involves input affecting two transitions with opposing effects on readout production.

Conclusions:

Output decoupling can arise from rate scale separation or incoherent regulation.
Incoherent regulation, a plausible TF regulatory mode, may be characterized by output decoupling.
Provides a framework for understanding output decoupling in input-output systems.