Cellular self-organization orchestrates ferroptosis propagation.

Cellular self-organization constrains the spread of ferroptosis, an iron-dependent oxidative cell death that can propagate as unbounded trigger waves. Low-density, misaligned regions with elevated YAP/TEAD1 activity are ferroptosis-sensitive, while high-density, aligned regions with increased NRF2 expression form propagation-resistant boundaries. Cell elongation polarizes oxidizable lipids to the poles, creating peroxidation hotspots that direct propagation along cell alignment; modeling and pharmacological perturbations show these factors confine isotropic waves into anisotropic, spatially limited spread.