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Experimental and theoretical study of mitotic spindle orientation

Abstract

The architecture and adhesiveness of a cell microenvironment is a critical factor for the regulation of spindle orientation in vivo1,2. Using a combination of theory and experiments, we have investigated spindle orientation in HeLa (human) cells. Here we show that spindle orientation can be understood as the result of the action of cortical force generators, which interact with spindle microtubules and are activated by cortical cues. We develop a simple physical description of this spindle mechanics, which allows us to calculate angular profiles of the torque acting on the spindle, as well as the angular distribution of spindle orientations. Our model accounts for the preferred spindle orientation and the shape of the full angular distribution of spindle orientations observed in a large variety of different cellular microenvironment geometries. It also correctly describes asymmetric spindle orientations, which are observed for certain distributions of cortical cues. We conclude that, on the basis of a few simple assumptions, we can provide a quantitative description of the spindle orientation of adherent cells.

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Figure 1: Mitotic spindle orientation and cortical forces.
Figure 2: Spindle orientation on adhesive micropatterns, showing theoretical results and experimental data.
Figure 3: Spindle orientation changes induced by continuous displacements of cortical cues.
Figure 4: Transition from symmetric to asymmetric spindle orientation.

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Acknowledgements

Acknowledgments We thank A. Pépin and Y. Chen for technical help with micropattern fabrication, J.-B. Sibarita for technical help with video-microscopy, D. Grunwald for technical help with confocal image acquisitions and Y. Bellaïche for discussions.

Author Contributions M.T. performed experimental work, A.J.-D. performed numerical calculations, V.R. designed the software for movie analyses, and M.T., A.J.-D., M.B. and F.J. conceived the theoretical model.

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Correspondence to Michel Bornens or Frank Jülicher.

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This file contains Supplementary Text with the full description of the model, Supplementary Discussion, Supplementary Figures S1- S3 with Legends and additional references. (PDF 1546 kb)

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Théry, M., Jiménez-Dalmaroni, A., Racine, V. et al. Experimental and theoretical study of mitotic spindle orientation. Nature 447, 493–496 (2007). https://doi.org/10.1038/nature05786

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