Thesis defense of Matthias Schmidt

Microtubules are hollow cylindrical filaments that are part of the cytoskeleton. During their growth, they exhibit “dynamic instability”, i.e., they can suddenly switch from growing to shrinking (catastrophe) and vice versa (rescue). Obtaining a microscopic understanding of this dynamic instability will also provide a better insight into basic cell functions like cell division and can provide a pathway to manipulate such processes. We introduce and parameterize a microtubule model that combines a mechanical, three-dimensional model of the microtubule's structure with the chemical processes happening during its growth. These chemical processes are the polymerization and depolymerization of tubulin dimers, the building blocks of microtubules, the formation and rupture of lateral bonds between neighboring tubulin monomers, and random hydrolysis. By ensuring that the simulation is computationally efficient despite the need for energy minimizations after each event, we are able to simulate microtubule growth for realistic timescales to observe catastrophes and rescues. In addition to analyzing different properties of the simulated microtubules and investigating the effects of dilution, i.e., the sudden decrease of the concentration of free tubulin dimers around the microtubule, we also consider mechanical feedback on the hydrolysis rate. We find this mechanical feedback to result in an effective anti-vectorial hydrolysis mechanism and that there are GTP-tubulin dimers much further away from the microtubule's plus end.

Thesis of Matthias Schmidt (2020): Chemomechanical Simulation of Microtubule Dynamics

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