A dynamic mechanical framework unmasks the ultrastructural and fluid-solid remodeling during myocardial infarction progression

Myocardial infarction (MI) triggers multiscale remodeling that changes the mechanical environment of the heart, but conventional stiffness measurements fail to capture the dynamic behavior of fluid-saturated tissue. Here, we developed a multiscale poro-viscoelastic framework to characterize MI-associated mechanical remodeling in murine myocardium. By combining power-law rheology with poro-elasticity theory, we resolved AFM creep responses into complementary markers of tissue state: the short-time power-law exponent ( α short ), the long-time power-law exponent ( α long ), the hydraulic permeability ( D ), the fluid–solid transition time ( τ ) and the elastic modulus ( E ). These mechanical signatures capture the delicate poro-viscoelastic alterations during MI: week-1 infarcts softened while the median D increased more than six-fold, consistent with edema and necrotic pore expansion. At week2, D fell below the control value and spatial heterogeneity was maximal, whereas week-4 scars were stiff, consolidated and characterized by persistently low D , a shortened fluid-like creep regime and a reduced long-time exponent. Integrating the poro-viscoelastic parameters improved cross-validated separation of early and chronic remodeling relative to stiffness alone, including an increase in AUC from 0.69 to 0.90 for control vs. week 1. These findings support dynamic fluid–solid mechanics as a quantitative framework for characterizing post-infarction remodeling and for defining mechanical benchmarks for cardiac regenerative biomaterials.