Computational modeling of microtubule dynamic instability: From molecular mechanisms to emergent behavior

Microtubule dynamic instability-the stochastic switching between growth, shortening, and pausing-is essential for cytoskeletal organization and cellular function. Despite decades of experimental and theoretical work, its molecular mechanism remains unresolved. In this review, we organize existing models based on their underlying conceptual framework and physical assumptions. We first discuss GTP-cap-based models, including stochastic GTP-cap models, mechanical-cap models, and lattice-as-allosteric-effector models, highlighting how different microscopic assumptions and computational implementations lead to distinct explanations of dynamic-instability processes, especially catastrophe. We then present a tubulin energy landscape framework in which dynamic instability emerges from nonequilibrium transitions of tubulin subunits among three experimentally characterized conformations constrained by lattice geometry. This approach provides a unified explanation for the full spectrum of dynamic instability behaviors, including growth, shortening, catastrophe, rescue, pausing, and distinct kinetics at the plus and minus ends. By making assumptions explicit, this review aims to clarify the physical logic underlying dynamic instability and provide a coherent foundation for future experimental and theoretical work.