Physical forces determining the persistency and centring precision of microtubule asters

Abstract

In early embryos, microtubules form star-shaped aster structures that can measure up to hundreds of micrometres in size, and move at high speeds to find the geometrical centre of the cell. This process, known as aster centration, is essential for the fidelity of cell division and development, but how cells succeed in moving these large structures through their crowded and fluctuating cytoplasm remains unclear. Here, we demonstrate that the positional fluctuations of migrating sea urchin sperm asters are small, anisotropic, and associated with the stochasticity of dynein-dependent forces moving the aster. Using in vivo magnetic tweezers to directly measure aster forces inside cells, we derive a linear aster force–velocity relationship and provide evidence for a spring-like active mechanism stabilizing the transverse position of the asters. The large frictional coefficient and spring constant quantitatively account for the amplitude and growth characteristics of athermal positional fluctuations, demonstrating that aster mechanics ensure noise suppression to promote persistent and precise centration. These findings define generic biophysical regimes of active cytoskeletal mechanics underlying the accuracy of cell division and early embryonic development.

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Fig. 1: Fluctuation analysis of centring microtubule asters.
Fig. 2: Force–velocity relationships of microtubule asters.
Fig. 3: Direct demonstration of a transverse feedback stabilizing asters along their centring direction.
Fig. 4: Aster mechanics ensure fast, persistent and precise aster centration.

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Acknowledgements

The authors acknowledge M. Coppey and J. Azimzadeh for technical support, and S. Dmitrieff, T. Strick, M. Piel, M. Thery and K. Laband for careful reading of the manuscript. This research was supported by the CNRS and grants from the ‘Mairie de Paris emergence’ program, the FRM ‘amorçage’ grant AJE20130426890 and the European Research Council (CoG Forcaster N° 647073).

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Contributions

H.T., L.D., J.S. and N.M. performed experiments. H.T. analysed the data and developed the model. H.T. and N.M. designed the research and wrote the manuscript.

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Correspondence to Nicolas Minc.

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Supplementary information

Supplementary Information

Supplementary model details, Supplementary References 1–3, Supplementary Figures 1–13

Reporting Summary

Supplementary Movie 1

Time-lapse of sperm aster centration imaged at 20 Hz in single plane on a spinning disk microscope. Cropping and rotation is done to orient centration from left to right

Supplementary Movie 2

In vivo magnetic force application against the centring motion of sperm asters. In this movie, the magnet is moved to two different position to change the amplitude of the force applied

Supplementary Movie 3

In vivo magnetic force application along the centring motion of sperm asters

Supplementary Movie 4

In vivo magnetic force application along the axis transverse to the centring motion of sperm asters. In this movie the force is released when the magnet tip disappears from the field of view. Following force cessation the aster comes back to the centration axis

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Tanimoto, H., Sallé, J., Dodin, L. et al. Physical forces determining the persistency and centring precision of microtubule asters. Nature Phys 14, 848–854 (2018). https://doi.org/10.1038/s41567-018-0154-4

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