Microtubules are the backbone of the cytoskeleton and vital to numerous cellular processes. The central dogma of microtubules is that all their functions are driven by dynamic instability, but its mechanism has remained unresolved for over 30 years because of conceptual difficulties inherent in the dominant GTP-cap framework. We present a physically rigorous structural mechanochemical model: dynamic instability is driven by non-equilibrium transitions between the bent (B), straight (S), and curved (C) forms of tubulin monomers and longitudinal interfaces in the two-dimensional lattice of microtubule. All the different phenomena (growth, shortening, catastrophe, rescue, and pausing) are controlled by the kinetic pathways for $\text{B}\leftrightarrow \text{S}\leftrightarrow \text{C}$ transitions and corresponding energy landscapes. Different kinetics at minus end are due to different $\text{B}\leftrightarrow \text{S}\leftrightarrow \text{C}$ pathways imposed by the polarity of microtubule lattice. This model enables us to reproduce all the observed phenomena of dynamic instability of purified tubulins in kinetic simulations.

微管是细胞骨架的支柱，对许多细胞过程至关重要。微管的中心法则是它们的所有功能都是由动态不稳定性驱动的，但由于占主导地位的 GTP-cap 框架固有的概念困难，其机制在 30 多年来仍未得到解决。我们提出了一个物理上严格的结构机械化学模型：动态不稳定性是由弯曲 (B)、直线 (S) 和弯曲 (C) 形式的微管蛋白单体和微管二维晶格中的纵向界面之间的非平衡转变驱动的. 所有不同的现象（增长、缩短、灾难、拯救和暂停）都由$\text{乙}\leftrightarrow \text{秒}\leftrightarrow \text{C}$转变和相应的能源景观。负端的不同动力学是由于不同的$\text{乙}\leftrightarrow \text{秒}\leftrightarrow \text{C}$由微管晶格的极性强加的通路。该模型使我们能够在动力学模拟中重现所有观察到的纯化微管蛋白的动态不稳定性现象。