Infarct border-zone biomechanics after myocardial infarction: linking mechanotransduction, fibrosis, and ventricular dysfunction.

Myocardial infarction (MI) transforms the left ventricle into a mechanically heterogeneous, evolving composite in which necrotic scar, viable myocardium, edema, microvascular injury, and fibro-inflammatory remodeling coexist. The infarct border zone is the decisive interface of this composite: a region in which surviving myocytes and stressed extracellular matrix (ECM) share load, exchange signals, and progressively reshape one another. Clinically, border-zone phenotype helps explain why patients with similar infarct size diverge toward recovery or progressive remodeling, heart failure, and arrhythmia. Mechanistically, the border zone concentrates "demand" through stress, strain, stress gradients, and shear generated by tethering between contracting remote myocardium and noncontracting or weakly contracting infarct core, by evolving thickness and curvature, and by stiffness gradients that change as edema resolves and collagen networks form and mature. Simultaneously, it determines "capacity" by governing matrix continuity, collagen alignment and cross-linking, and myocyte-ECM coupling that together set stiffness, strength, and tearing resistance, which are not interchangeable and can evolve in different directions. This review synthesizes border-zone biomechanics across scales, integrating histology, echocardiographic strain, cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) and mapping, diffusion and microstructure imaging, and patient-specific computational cardiomechanics. We connect abnormal border-zone deformation to mechanosensing in myocytes, fibroblasts, endothelial cells, and immune cells via integrins, focal adhesion signaling, stretch-activated channels, cytoskeletal remodeling, and transcriptional regulators including YAP/TAZ and MRTF, and we interpret fibrosis architecture as a mechanically regulated "record" of cumulative loading history. We then evaluate evidence linking border-zone strain patterns, stiffness gradients, microvascular obstruction, and intramyocardial hemorrhage to remodeling trajectory and electrical instability, explicitly distinguishing association, prediction, and causation. Finally, we outline translational requirements for a clinically deployable border-zone risk phenotype that combines imaging with inverse modeling and uncertainty quantification, and we propose testable hypotheses that can be validated in prospective cohorts. A mechanics-first view of the border zone reframes post-MI remodeling as an interface problem and provides a disciplined basis for mechanomodulatory therapies that unload, reinforce, or reprogram the peri-infarct microenvironment.