Mechanical fracturing of the extracellular matrix patterns the vertebrate heart

Trabeculation, the process where cardiomyocytes delaminate to form ventricular ridges essential for circulation, is a critical step during heart development. While previously attributed only to biochemical prepatterning, we demonstrate that trabeculation is instead guided by mechanical fracturing of the cardiac extracellular matrix (cECM), induced by myocardial contractions. The heart’s anisotropic curvature directs mechanical stress, leading to spatially patterned cECM fractures that serve as structural cues for trabeculation. To investigate this mechanism, we quantify the strain produced by the myocardial layer and develop a biophysical mathematical model that simulates cECM dynamics under cyclic cardiac beating. Using computational simulations on a 3D reconstruction of the myocardium, we predict fracture patterns based on tissue geometry and material properties, matching experimental observations in zebrafish embryos. These findings establish mechanical fracturing as a direct morphogenetic driver of trabeculation, challenging the paradigm that biochemical signals alone dictate ventricular patterning. More broadly, our work underscores how tissue geometry and mechanical forces actively shape cardiac development, reinforcing a self-organizing principle in morphogenesis.