Thesis presented June 14, 2021

Abstract:
Common textbook knowledge states that the microtubule elongates and shortens only at the tip, where it displays a dynamic instability. Recently, we discovered that the microtubule shows unexpected dynamics along the lattice region offering new regulatory mechanisms of microtubule stability. Our working hypothesis is that structural defects in the microtubule lattice fosters the exchange of dimers.
We developed strategies to visualize and quantify these dynamics. We modulated the amount of defects in the microtubule lattice, measured the impact on dimer turnover along the microtubule and found that, by increasing the elongation speed, we increase the defects frequency.
In vivo, microtubule functions depend on proteins associated to it (MAPs). For instance, molecular motors play a key role inside cells and have a strong impact on microtubule dynamics, especially at their tips. During my thesis, I aimed to understand how such motors could affect the inside dynamics of microtubules all along their lattice.
I have shown that, by walking on an un-stabilized lattice, molecular motors such as kinesines and dyneins are able to create and amplify existing defects, thus provoking fast microtubule collapse, or microtubule renewal if there is free tubulin in the medium.
This finding allows us to assume there is microtubule lattice dynamics, involving dimers exchanges and microtubules rejuvenation, inside physiological systems.

Keywords:
kinesin, rejuvenation, repair, microtubule, MAP, Micropatterning, in vitro reconstitution, Microfluidics, molecular motor

On-line thesis.