Metastasis of cancer cells is closely associated with their ability to undergo mechanical softening under shear stress. A statistical-thermodynamic model has been developed to demonstrate the crucial role of entropic effects in this process. The model establishes a quantitative relationship between the reorganization of the cytoskeleton's orientation and alterations in mechanical properties, as well as entropy production. This elucidates the phenomenon of mechanical softening in cells under loads ranging from 0.09 to 0.63 Pa. The validation of the model was undertaken using experimental data from A431 cells, which demonstrated high accuracy (root mean square error of 0.0069) and noise resistance. Thermodynamic analysis revealed a nonlinear relationship between entropy production and orientation deformation. It is proposed that a new marker for metastatic potential be established, with the marker being defined as “dissipative process frequency.” This parameter demonstrates remarkable stability across different loading conditions (variation of 7.35%). The reliability of the marker was confirmed through Monte Carlo simulations, which yielded a coefficient of variation of less than 12.1%. The present study establishes a fundamental connection between cytoskeletal thermodynamics and the mechanical properties of cancer cells, offering novel opportunities for metastasis diagnosis based on dissipative characteristics.

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• Cancer
• Mechanobiology
• Nonequilibrium statistical mechanics
• Cells