Atomistic Basis of Microtubule Dynamic Instability Assessed Via Multiscale Modeling

• Published in: Annals of biomedical engineering 2021-07, Vol.49 (7), p.1716-1734
• Main Authors: Hemmat, Mahya, Odde, David J.
• Format: Article
• Language: English
• Subjects: Atomic structure; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biomedical engineering; Biomedical Engineering and Bioengineering; Biomedicine; Biophysics; Cell division; Cellular structure; Classical Mechanics; Dynamic stability; Electron microscopy; Engineering; Guanosine Diphosphate - chemistry; Guanosine Diphosphate - metabolism; Guanosine triphosphate; Guanosine Triphosphate - chemistry; Guanosine Triphosphate - metabolism; Hydrolysis; Instability; Microscopy; Microtubules - chemistry; Mitosis; Modelling; Molecular Dynamics Simulation; Original; Original Article; Simulation; Stability analysis; Tubulin; Tubulin - chemistry; Tubulin - metabolism
• ISSN: 0090-6964; 1573-9686
• DOI: 10.1007/s10439-020-02715-6

Microtubule “dynamic instability,” the abrupt switching from assembly to disassembly caused by the hydrolysis of GTP to GDP within the β subunit of the αβ-tubulin heterodimer, is necessary for vital cellular processes such as mitosis and migration. Despite existing high-resolution structural data, the key mechanochemical differences between the GTP and GDP states that mediate dynamic instability behavior remain unclear. Starting with a published atomic-level structure as an input, we used multiscale modeling to find that GTP hydrolysis results in both longitudinal bond weakening (~ 4 k B T ) and an outward bending preference (~ 1.5 k B T ) to both drive dynamic instability and give rise to the microtubule tip structures previously observed by light and electron microscopy. More generally, our study provides an example where atomic level structural information is used as the sole input to predict cellular level dynamics without parameter adjustment.