Cell Behavior Science (CBS): A Physically Grounded Framework Integrating Non-Equilibrium Thermodynamics, Active Matter Theory, Mechanobiology, Gene Regulatory Networks, Metabolic Fluxes, and Extracellular Matrix Remodeling

We present Cell Behavior Science (CBS), a predictive framework grounded in physics that rigorously integrates non-equilibrium thermodynamics, active matter hydrodynamics, cytoskeletal mechanobiology, gene regulatory networks (GRNs), metabolic fluxes, and extracellular matrix (ECM) remodeling to quantitatively model cellular dynamics across ontogenesis, homeostasis, and pathology. CBS treats the cell as an open, far-from-equilibrium dissipative system driven by ATP hydrolysis, constrained by stochastic thermodynamics, with explicit bidirectional feedbacks from constraint-based metabolic optimization and durotactic ECM evolution. Two empirically falsifiable hypotheses anchor the framework: (1) Coherent Vibrational Network (CVN), ultrafast anharmonic oscillations (10 fs–1 ps) in hydrophobic protein cores enabling energy delocalization, validated by 2D-IR spectroscopy; (2) Mechano-Geometric Memory (MGM), prestressed cytoskeletal lattices encoding mechanical histories in low-frequency eigenmodes, quantifiable via traction force microscopy and ATAC-seq.Unified in the Entropic Flux Model (EFM), a continuum theory precisely quantifying local entropy reduction through ATP dissipation, incorporating mechanotransductive feedbacks via Rho GTPases and YAP/TAZ, dynamic metabolic balances, and ECM kinetics. EFM upholds the second law globally while permitting transient negentropic domains via dissipative fluxes.Hybrid ABM-GNN implementation, parameterized on synthetic/empirical datasets, yields 85–91% predictive fidelity in tumor invasion, organoid engraftment, and resistance phylogenies, surpassing baselines by 12–28% in RMSE, AUC, and accuracy.All resources MIT-licensed for reproducibility. CBS furnishes a falsifiable scaffold for predictive biophysics from quanta to tissues, with extensions to precision medicine applications including personalized cancer therapy, regenerative scaffolds, and digital twins.Keywords: Non-equilibrium thermodynamics; Active matter hydrodynamics; Mechanotransduction; Stochastic thermodynamics; Gene regulatory networks; Metabolic flux balance; Extracellular matrix remodeling; Cellular dynamics; Graph neural networks; Agent-based modeling; Precision medicine