Abstract
We introduce and parameterize a chemomechanical model of microtubule dynamics on the dimer level, which is based on the allosteric tubulin model and includes attachment, detachment and hydrolysis of tubulin dimers as well as stretching of lateral bonds, bending at longitudinal junctions, and the possibility of lateral bond rupture and formation. The model is computationally efficient such that we reach sufficiently long simulation times to observe repeated catastrophe and rescue events at realistic tubulin concentrations and hydrolysis rates, which allows us to deduce catastrophe and rescue rates. The chemomechanical model also allows us to gain insight into microscopic features of the GTP-tubulin cap structure and microscopic structural features triggering microtubule catastrophes and rescues. Dilution simulations show qualitative agreement with experiments. We also explore the consequences of a possible feedback of mechanical forces onto the hydrolysis process and the GTP-tubulin cap structure.
Highlights
Microtubule (MT) dynamics is essential for many cellular processes, such as the positioning and separation of chromosomes in mitosis [1], or maintenance of cell polarity and cell shape [2]
In reference [18], where mechanics was implemented via full Brownian dynamics, only short times scales could be reached
If hydrolysis is coupled to mechanics, the spatial distribution is only exponential in its tail, has larger values at the MT tip, and GTP-tubulin dimers can be found much deeper in the GDP-body
Summary
Microtubule (MT) dynamics is essential for many cellular processes, such as the positioning and separation of chromosomes in mitosis [1], or maintenance of cell polarity and cell shape [2]. Hydrolysis of tubulin dimers embedded in a straight MT causes mechanical strains in the tubular structure because the surrounding MT lattice prevents these GDP-tubulin dimers from assuming their preferred bent conformation This mechanical strain is released in a catastrophe via the rupture of lateral bonds. The lattice model, on the other hand, is based on evidence from X-ray and cryo-EM structures [20,21,22,23] and simulations [24, 25] that GTP-tubulin dimers assume a bent conformation and that hydrolysis rather affects the lateral and longitudinal dimer interaction energies The model by Margolin et al [33] has successfully reproduced features of the experimentally observed MT dynamic instability [35] but relies on a heuristic tuning of simulation parameters
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