Beyond biochemical patterning: How mechanical bistability governs robust organoid morphogenesis

Understanding the regulatory mechanisms of intestinal organoid morphogenesis remains a fundamental challenge in organoid biology. Emerging evidence highlights mechanical bistability as a critical regulator, mediated by dynamic lumen-actomyosin feedback. The recently developed 3D vertex model demonstrates that crypt curvature modulates actomyosin localization via mechanosensitive pathways, creating two stable morphological states—bulged or budded—depending on mechanical history. This model advances beyond static vertex models by incorporating epithelial thickness variations and lumen pressure effects, explaining previously unresolved phenomena like irreversible crypt budding and snap-through transitions. The findings establish a new framework for understanding mechanical decision-making in epithelial tissues, with implications for organoid engineering and developmental biology.