Journal Article

Genomic-Thermodynamic Phase Synchronization: Maxwell’s Demon-like Regulation of Cell Fate Transition

Giuliani, Alessandro, Yoshikawa, Kenichi, Tsuchiya, Masa

2025

Overview

Dynamic criticality—the balance between order and chaos—is fundamental to genome regulation and cellular transitions. In this study, we investigate the distinct behaviors of gene expression dynamics in MCF-7 breast cancer cells under two stimuli: heregulin (HRG), which promotes cell fate transitions, and epidermal growth factor (EGF), which binds to the same receptor but fails to induce cell-fate changes. We model the system as an open, nonequilibrium thermodynamic system and introduce a convergence-based approach for the robust estimation of information-thermodynamic metrics. Our analysis reveals that the Shannon entropy of the critical point (CP) dynamically synchronizes with the entropy of the rest of the whole expression system (WES), reflecting coordinated transitions between ordered and disordered phases. This phase synchronization is driven by net mutual information scaling with CP entropy dynamics, demonstrating how the CP governs genome-wide coherence. Furthermore, higher-order mutual information emerges as a defining feature of the nonlinear gene expression network, capturing collective effects beyond simple pairwise interactions. By achieving thermodynamic phase synchronization, the CP orchestrates the entire expression system. Under HRG stimulation, the CP becomes active, functioning as a Maxwell’s demon with dynamic, rewritable chromatin memory to guide a critical transition in cell fate. In contrast, under EGF stimulation, the CP remains inactive in this strategic role, passively facilitating a non-critical transition. These findings establish a biophysical framework for cell fate determination, paving the way for innovative approaches in cancer research and stem cell therapy.

• Publisher: MDPI AG,MDPI
• Subject: Analysis / Breast Neoplasms - genetics / Breast Neoplasms - metabolism / Breast Neoplasms - pathology / Cancer / Cell Differentiation - genetics / Dynamical systems / Entropy / Epidermal growth factor / Epidermal Growth Factor - metabolism / Epidermal Growth Factor - pharmacology / Equilibrium / Female / Gene expression / Gene Expression Regulation, Neoplastic / Gene Regulatory Networks / Genes / Genomes / Genomics / Humans / Maxwell, James Clerk / MCF-7 Cells / Neuregulin-1 - metabolism / Neuregulin-1 - pharmacology / Open systems / Thermodynamics