Unifying Non-Equilibrium Information Thermodynamics and Genome Engine Dynamics: Maxwell's Demon Control of Cancer Cell Fates

Abstract

Molecular biology has revealed immense spatiotemporal complexity in cancer regulatory networks. A fundamental physical question remains: Does a physical principle exist that governs how this complexity self-organizes into genome-wide fate commitment and determines whether and when that commitment becomes irreversible? We address this question through an integrative biophysical analysis of time-series transcriptomes from two cancer systems under four conditions: MCF-7 human breast cancer cells stimulated with heregulin (HRG) or epidermal growth factor (EGF), and HL-60 human leukemia cells stimulated with all-trans retinoic acid (atRA) or dimethyl sulfoxide (DMSO). Our analysis establishes self-organized criticality (SOC) control as a biophysical principle that unifies information thermodynamics with genome-engine dynamics in a single open, non-equilibrium physical system. This principle elucidates how information processing is converted into mechanical work during cancer-fate commitment. Under SOC control, the genome operates as an open, non-equilibrium engine that maintains a critical dynamic balance between homeostatic stability and fate-guiding critical transitions. The critical point (CP) gene ensemble drives this genome-wide control. Within the environment-coupled whole expression system, the CP performs two coupled roles converging in a Maxwells demon (MD) actuation cycle. This cycle is implemented through rewritable chromatin memory exhibiting bistable switching. Thermodynamically, the CP acts as an MD operator regulating entropy and information-work conversion through phase synchronization. Dynamically, it acts as an SOC controller synchronizing with the genome attractor, driving genome-wide reorganization, and generating the dominant mechanical work. This unified mechanism distinguishes the rapid HRG, delayed DMSO, and two-step atRA commitments from the non-committing EGF response. It satisfies three open-system thermodynamic criteria for an irreversible arrow of time and defines time-gated rules with predictive intervention windows for dynamic cancer-fate control.