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Auteur principal: Simao, Eugenio
Format: Preprint
Publié: 2026
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Accès en ligne:https://arxiv.org/abs/2601.04335
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author Simao, Eugenio
author_facet Simao, Eugenio
contents Cellular decision-making under stress involves rapid pathway selection despite energy scarcity. Here we demonstrate that thermodynamic constraints actively drive energy-efficient sporulation, where continuous metabolic sources enable system robustness through dynamic energy management. Using hybrid Petri nets (stochastic transitions with continuous sources) to model Bacillus subtilis sporulation, we show that stress conditions (ATP = 300 mM, 94% depletion) enable sporulation completion with extreme energy efficiency: 0.73 mM ATP per mature spore versus 11.6 mM ATP under normal conditions--a 16-fold efficiency gain. Despite ATP dropping to 1 mM (99.7% depletion) during the crisis, continuous ATP regeneration rescues the system, producing 67 mM mature spores (89% of normal yield) with only 49 mM total ATP consumption. This efficiency emerges from the interplay between stochastic regulatory transitions and continuous metabolic sources, where GTP accumulation (+4974 mM, 166% increase) provides an energy buffer while ATP regeneration (+240 mM) prevents complete depletion. The hybrid Petri net formalism--combining stochastic transitions for regulatory events with continuous sources for metabolic flux--extended with thermodynamic constraints through inhibitor arcs and energy-coupled rate functions, provides the mathematical foundation enabling this discovery by integrating discrete regulatory logic with continuous energy dynamics in a resource-aware concurrency model.
format Preprint
id arxiv_https___arxiv_org_abs_2601_04335
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Thermodynamic Constraints Drive Hierarchical Preemption in Cellular Decision-Making: A Hybrid Petri Net Framework with Application to Bacillus subtilis Sporulation
Simao, Eugenio
Molecular Networks
Cell Behavior
Genomics
Subcellular Processes
92C42, 92C40, 80A30, 68Q85
I.6.3; I.6.5; G.3; F.1.2
Cellular decision-making under stress involves rapid pathway selection despite energy scarcity. Here we demonstrate that thermodynamic constraints actively drive energy-efficient sporulation, where continuous metabolic sources enable system robustness through dynamic energy management. Using hybrid Petri nets (stochastic transitions with continuous sources) to model Bacillus subtilis sporulation, we show that stress conditions (ATP = 300 mM, 94% depletion) enable sporulation completion with extreme energy efficiency: 0.73 mM ATP per mature spore versus 11.6 mM ATP under normal conditions--a 16-fold efficiency gain. Despite ATP dropping to 1 mM (99.7% depletion) during the crisis, continuous ATP regeneration rescues the system, producing 67 mM mature spores (89% of normal yield) with only 49 mM total ATP consumption. This efficiency emerges from the interplay between stochastic regulatory transitions and continuous metabolic sources, where GTP accumulation (+4974 mM, 166% increase) provides an energy buffer while ATP regeneration (+240 mM) prevents complete depletion. The hybrid Petri net formalism--combining stochastic transitions for regulatory events with continuous sources for metabolic flux--extended with thermodynamic constraints through inhibitor arcs and energy-coupled rate functions, provides the mathematical foundation enabling this discovery by integrating discrete regulatory logic with continuous energy dynamics in a resource-aware concurrency model.
title Thermodynamic Constraints Drive Hierarchical Preemption in Cellular Decision-Making: A Hybrid Petri Net Framework with Application to Bacillus subtilis Sporulation
topic Molecular Networks
Cell Behavior
Genomics
Subcellular Processes
92C42, 92C40, 80A30, 68Q85
I.6.3; I.6.5; G.3; F.1.2
url https://arxiv.org/abs/2601.04335