Mechanical properties of a complete microtubule revealed through molecular dynamics simulation

David B. Wells, and Aleksei Aksimentiev
Biophys J 99(2) 629-37 (2010)
DOI:10.1016/j.bpj.2010.04.038  PMID:20643083  BibTex


Microtubules are ubiquitous biological filaments found in all eukaryotic cells. They are the largest type of cellular filament, and are essential in processes ranging from mitosis and meiosis to flaggelar motility. Due to their structural importance, the mechanical properties of microtubules have been extensively studied. However, because of the small size of microtubules and their high rigidity, experimental studies have determined the Young's modulus only indirectly. Molecular dynamics (MD) simulations allows the elastic properties of a biopolymer to be determined computationally. However, while the atomic structures of the building blocks of a microtubule (α- and β-tubulin) have been solved, the only published structures of a complete microtubule are cryo-electron microscopy maps far from atomic resolution. Using the cryo-EM map as a guide, we have produced the first all-atom structure of a complete microtubule. With this model, we applied tension, compression, and shear to determine the elastic moduli of an effectively infinite microtubule, yielding results in agreement with previous estimates. This work is one of the first to combine cryo-EM and crystallographic structures for subsequent all-atom MD simulation. The successful performance of such a model opens the door to the simulation of many other systems whose constituent units are known in atomic detail but whose complete structure is known only at lower resolution.


Microtubules (MTs) are the largest type of cellular filament, essential in processes ranging from mitosis and meiosis to flagellar motility. Many of the processes depend critically on the mechanical properties of the MT, but the elastic moduli, notably the Young's modulus, are not directly revealed in experiment, which instead measures either flexural rigidity or response to radial deformation. Molecular dynamics (MD) is a method that allows the mechanical properties of single biomolecules to be investigated through computation. Typically, MD requires an atomic resolution structure of the molecule, which is unavailable for many systems, including MTs. By combining structural information from cryo-electron microscopy and electron crystallography, we have constructed an all-atom model of a complete MT and used MD to determine its mechanical properties. The simulations revealed nonlinear axial stress-strain behavior featuring a pronounced softening under extension, a possible plastic deformation transition under radial compression, and a distinct asymmetry in response to the two senses of twist. This work demonstrates the possibility of combining different levels of structural information to produce all-atom models suitable for quantitative MD simulations, which extends the range of systems amenable to the MD method and should enable exciting advances in our microscopic knowledge of biology.