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Lattice defects induce microtubule self-renewal

Abstract

Microtubules are dynamic polymers, which grow and shrink by addition and removal of tubulin dimers at their extremities. Within the microtubule shaft, dimers adopt a densely packed and highly ordered crystal-like lattice structure, which is generally not considered to be dynamic. Here, we report that thermal forces are sufficient to remodel the microtubule shaft, despite its apparent stability. Our combined experimental data and numerical simulations on lattice dynamics and structure suggest that dimers can spontaneously leave and be incorporated into the lattice at structural defects. We propose a model mechanism, where the lattice dynamics is initiated via a passive breathing mechanism at dislocations, which are frequent in rapidly growing microtubules. These results show that we may need to extend the concept of dissipative dynamics, previously established for microtubule extremities, to the entire shaft, instead of considering it as a passive material.

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Data availability

The data that support the findings of this study are available from the authors upon reasonable request, see author contributions for specific datasets.

Code availability

The source code of the kinetic Monte Carlo model along with detailed instructions to reproduce the data for this manuscript is available online (https://sourceforge.net/projects/microtubulelatticemodel). The codes for the analysis of the model simulations are available from the corresponding authors upon request.

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Acknowledgements

This work was supported by the French National Agency for Research (ANR-16-CE11-0017-01 to D.C., ANR-12-BSV5-0004-01 to M.T., ANR-14-CE09-0014-02 to L.B. and ANR-18-CE13-0001 to K.J., M.T. and D.C.), the Human Frontier in Science Program (RGY0088 to M.T.) and the European Research Council (Consolidator Grant 771599 (ICEBERG) to M.T. and Advanced Grant 741773 (AAA) to L.B.).

Author information

L.S. and S.T. performed all dimer exchange and fracture experiments with the help of J.G. and A.A. L.S., L.B. and M.T. designed these experiments. D.C. designed and performed cryo-electron microscopy experiments. K.J. designed and performed numerical simulations. L.S., S.T., C.A., L.B., M.T. and K.J. analysed data. L.S., M.T., D.C. and K.J. wrote the manuscript.

Competing interests

The authors declare no competing interests.

Correspondence to Laurent Blanchoin or Manuel Théry or Karin John.

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Supplementary Information

Supplementary Information, Supplementary Methods, Supplementary Figs. 1–8, Supplementary Tables 1 and 2, and Supplementary References 1–19.

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Fig. 1: Incorporation of free tubulin into the microtubule lattice visualized by TIRF.
Fig. 2: Monte Carlo simulations of microtubule lattice dynamics.
Fig. 3: Dislocation defects in the microtubule lattice detected by cryo-electron microscopy.
Fig. 4: Incorporation of free tubulin into the microtubule lattice visualized by TIRF.
Fig. 5