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Interplay of condensate material properties and chromatin heterogeneity governs nuclear condensate ripening

Deb Sankar Banerjee, Tafadzwa Chigumira, Rachel M. Lackner, Josiah C. Kratz, David M. Chenoweth, Shiladitya Banerjee, View ORCID ProfileHuaiying Zhang
doi: https://doi.org/10.1101/2024.05.07.593010
Deb Sankar Banerjee
1Department of Physics, Carnegie Mellon University, Pittsburgh, PA 15213, USA
2James Franck Institute, University of Chicago, Chicago, IL 60637, USA
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Tafadzwa Chigumira
3Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA
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Rachel M. Lackner
4Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104
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Josiah C. Kratz
5Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA
6Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA
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David M. Chenoweth
4Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104
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Shiladitya Banerjee
1Department of Physics, Carnegie Mellon University, Pittsburgh, PA 15213, USA
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  • For correspondence: [email protected] [email protected]
Huaiying Zhang
3Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA
5Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA
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  • ORCID record for Huaiying Zhang
  • For correspondence: [email protected] [email protected]
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Abstract

Nuclear condensates play many important roles in chromatin functions, but how cells regulate their nucleation and growth within the complex nuclear environment is not well understood. Here, we report how condensate properties and chromatin mechanics dictate condensate growth dynamics in the nucleus. We induced condensates with distinct properties using different proteins in human cell nuclei and monitored their growth. We revealed two key physical mechanisms that underlie droplet growth: diffusion-driven or ripening-dominated growth. To explain the experimental observations, we developed a quantitative theory that uncovers the mechanical role of chromatin and condensate material properties in regulating condensate growth in a heterogeneous environment. By fitting our theory to experimental data, we find that condensate surface tension is critical in determining whether condensates undergo elastic or Ostwald ripening. Our model also predicts that chromatin heterogeneity can influence condensate nucleation and growth, which we validated by experimentally perturbing the chromatin organization and controlling condensate nucleation. By combining quantitative experimentation with theoretical modeling, our work elucidates how condensate surface tension and chromatin heterogeneity govern nuclear condensate ripening, implying that cells can control both condensate properties and the chromatin organization to regulate condensate growth in the nucleus.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Abstract and Introduction were edited for clarity.

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 August 21, 2024.
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Interplay of condensate material properties and chromatin heterogeneity governs nuclear condensate ripening
Deb Sankar Banerjee, Tafadzwa Chigumira, Rachel M. Lackner, Josiah C. Kratz, David M. Chenoweth, Shiladitya Banerjee, Huaiying Zhang
bioRxiv 2024.05.07.593010; doi: https://doi.org/10.1101/2024.05.07.593010
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Interplay of condensate material properties and chromatin heterogeneity governs nuclear condensate ripening
Deb Sankar Banerjee, Tafadzwa Chigumira, Rachel M. Lackner, Josiah C. Kratz, David M. Chenoweth, Shiladitya Banerjee, Huaiying Zhang
bioRxiv 2024.05.07.593010; doi: https://doi.org/10.1101/2024.05.07.593010

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