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Mechanical frustration of phase separation in the cell nucleus by chromatin

View ORCID ProfileYaojun Zhang, View ORCID ProfileDaniel S.W. Lee, Yigal Meir, Clifford P. Brangwynne, View ORCID ProfileNed S. Wingreen
doi: https://doi.org/10.1101/2020.12.24.424222
Yaojun Zhang
1Department of Physics, Princeton University, Princeton, NJ 08544, USA
2Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA
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Daniel S.W. Lee
2Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA
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Yigal Meir
1Department of Physics, Princeton University, Princeton, NJ 08544, USA
3Department of Physics, Ben Gurion University of the Negev, Beer Sheva 84105, Israel
4Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
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Clifford P. Brangwynne
5Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA
6Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
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Ned S. Wingreen
2Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA
4Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
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  • For correspondence: wingreen@princeton.edu
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Abstract

Liquid-liquid phase separation is a fundamental mechanism underlying subcellular organization. Motivated by the striking observation that optogenetically-generated droplets in the nucleus display suppressed coarsening dynamics, we study the impact of chromatin mechanics on droplet phase separation. We combine theory and simulation to show that crosslinked chromatin can mechanically suppress droplets’ coalescence and ripening, as well as quantitatively control their number, size, and placement. Our results highlight the role of the subcellular mechanical environment on condensate regulation.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 24, 2020.
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Mechanical frustration of phase separation in the cell nucleus by chromatin
Yaojun Zhang, Daniel S.W. Lee, Yigal Meir, Clifford P. Brangwynne, Ned S. Wingreen
bioRxiv 2020.12.24.424222; doi: https://doi.org/10.1101/2020.12.24.424222
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Mechanical frustration of phase separation in the cell nucleus by chromatin
Yaojun Zhang, Daniel S.W. Lee, Yigal Meir, Clifford P. Brangwynne, Ned S. Wingreen
bioRxiv 2020.12.24.424222; doi: https://doi.org/10.1101/2020.12.24.424222

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