Chromatin network retards nucleoli coalescence
<jats:title>Abstract</jats:title><jats:p>Nuclear bodies are membraneless condensates that may form via liquid-liquid phase separation. The viscoelastic chromatin network could impact their stability and may hold the key for understanding experimental observations that defy predicti...
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| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2022
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| Online Access: | https://hdl.handle.net/1721.1/141349 |
| _version_ | 1826194215192756224 |
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| author | Qi, Yifeng Zhang, Bin |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Qi, Yifeng Zhang, Bin |
| author_sort | Qi, Yifeng |
| collection | MIT |
| description | <jats:title>Abstract</jats:title><jats:p>Nuclear bodies are membraneless condensates that may form via liquid-liquid phase separation. The viscoelastic chromatin network could impact their stability and may hold the key for understanding experimental observations that defy predictions of classical theories. However, quantitative studies on the role of the chromatin network in phase separation have remained challenging. Using a diploid human genome model parameterized with chromosome conformation capture (Hi-C) data, we study the thermodynamics and kinetics of nucleoli formation. Dynamical simulations predict the formation of multiple droplets for nucleolar particles that experience specific interactions with nucleolus-associated domains (NADs). Coarsening dynamics, surface tension, and coalescence kinetics of the simulated droplets are all in quantitative agreement with experimental measurements for nucleoli. Free energy calculations further support that a two-droplet state, often observed for nucleoli in somatic cells, is metastable and separated from the single-droplet state with an entropic barrier. Our study suggests that nucleoli-chromatin interactions facilitate droplets’ nucleation but hinder their coarsening due to the coupled motion between droplets and the chromatin network: as droplets coalesce, the chromatin network becomes increasingly constrained. Therefore, the chromatin network supports a nucleation and arrest mechanism to stabilize the multi-droplet state for nucleoli and possibly for other nuclear bodies.</jats:p> |
| first_indexed | 2024-09-23T09:52:40Z |
| format | Article |
| id | mit-1721.1/141349 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:52:40Z |
| publishDate | 2022 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1413492023-02-08T19:18:02Z Chromatin network retards nucleoli coalescence Qi, Yifeng Zhang, Bin Massachusetts Institute of Technology. Department of Chemistry <jats:title>Abstract</jats:title><jats:p>Nuclear bodies are membraneless condensates that may form via liquid-liquid phase separation. The viscoelastic chromatin network could impact their stability and may hold the key for understanding experimental observations that defy predictions of classical theories. However, quantitative studies on the role of the chromatin network in phase separation have remained challenging. Using a diploid human genome model parameterized with chromosome conformation capture (Hi-C) data, we study the thermodynamics and kinetics of nucleoli formation. Dynamical simulations predict the formation of multiple droplets for nucleolar particles that experience specific interactions with nucleolus-associated domains (NADs). Coarsening dynamics, surface tension, and coalescence kinetics of the simulated droplets are all in quantitative agreement with experimental measurements for nucleoli. Free energy calculations further support that a two-droplet state, often observed for nucleoli in somatic cells, is metastable and separated from the single-droplet state with an entropic barrier. Our study suggests that nucleoli-chromatin interactions facilitate droplets’ nucleation but hinder their coarsening due to the coupled motion between droplets and the chromatin network: as droplets coalesce, the chromatin network becomes increasingly constrained. Therefore, the chromatin network supports a nucleation and arrest mechanism to stabilize the multi-droplet state for nucleoli and possibly for other nuclear bodies.</jats:p> 2022-03-23T16:29:14Z 2022-03-23T16:29:14Z 2021-12 2022-03-23T16:25:54Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141349 Qi, Yifeng and Zhang, Bin. 2021. "Chromatin network retards nucleoli coalescence." Nature Communications, 12 (1). en 10.1038/s41467-021-27123-9 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Qi, Yifeng Zhang, Bin Chromatin network retards nucleoli coalescence |
| title | Chromatin network retards nucleoli coalescence |
| title_full | Chromatin network retards nucleoli coalescence |
| title_fullStr | Chromatin network retards nucleoli coalescence |
| title_full_unstemmed | Chromatin network retards nucleoli coalescence |
| title_short | Chromatin network retards nucleoli coalescence |
| title_sort | chromatin network retards nucleoli coalescence |
| url | https://hdl.handle.net/1721.1/141349 |
| work_keys_str_mv | AT qiyifeng chromatinnetworkretardsnucleolicoalescence AT zhangbin chromatinnetworkretardsnucleolicoalescence |