Liquid–Liquid Phase Separation in the Presence of Macromolecular Crowding and State-dependent Kinetics
Biomolecular condensates formed via liquid–liquid phase separation (LLPS) are increasingly being shown to play major roles in cellular self-organization dynamics in health and disease. It is well established that macromolecular crowding has a profound impact on protein interactions, particularly tho...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/6675 |
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| author | Alick-O. Vweza Chul-Gyu Song Kil-To Chong |
| author_facet | Alick-O. Vweza Chul-Gyu Song Kil-To Chong |
| author_sort | Alick-O. Vweza |
| collection | DOAJ |
| description | Biomolecular condensates formed via liquid–liquid phase separation (LLPS) are increasingly being shown to play major roles in cellular self-organization dynamics in health and disease. It is well established that macromolecular crowding has a profound impact on protein interactions, particularly those that lead to LLPS. Although synthetic crowding agents are used during in vitro LLPS experiments, they are considerably different from the highly crowded nucleo-/cytoplasm and the effects of in vivo crowding remain poorly understood. In this work, we applied computational modeling to investigate the effects of macromolecular crowding on LLPS. To include biologically relevant LLPS dynamics, we extended the conventional Cahn–Hilliard model for phase separation by coupling it to experimentally derived macromolecular crowding dynamics and state-dependent reaction kinetics. Through extensive field-theoretic computer simulations, we show that the inclusion of macromolecular crowding results in late-stage coarsening and the stabilization of relatively smaller condensates. At a high crowding concentration, there is an accelerated growth and late-stage arrest of droplet formation, effectively resulting in anomalous labyrinthine morphologies akin to protein gelation observed in experiments. These results not only elucidate the crowder effects observed in experiments, but also highlight the importance of including state-dependent kinetics in LLPS models, and may help in designing further experiments to probe the intricate roles played by LLPS in self-organization dynamics of cells. |
| first_indexed | 2024-03-10T10:10:28Z |
| format | Article |
| id | doaj.art-2ec00e1af57a4b3baf67bc21464e2fc7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:10:28Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2ec00e1af57a4b3baf67bc21464e2fc72023-11-22T01:12:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213667510.3390/ijms22136675Liquid–Liquid Phase Separation in the Presence of Macromolecular Crowding and State-dependent KineticsAlick-O. Vweza0Chul-Gyu Song1Kil-To Chong2Department of Electronics and Information Engineering, Jeonbuk National University, Jeonju 54896, KoreaDepartment of Electronics and Information Engineering, Jeonbuk National University, Jeonju 54896, KoreaDepartment of Electronics and Information Engineering, Jeonbuk National University, Jeonju 54896, KoreaBiomolecular condensates formed via liquid–liquid phase separation (LLPS) are increasingly being shown to play major roles in cellular self-organization dynamics in health and disease. It is well established that macromolecular crowding has a profound impact on protein interactions, particularly those that lead to LLPS. Although synthetic crowding agents are used during in vitro LLPS experiments, they are considerably different from the highly crowded nucleo-/cytoplasm and the effects of in vivo crowding remain poorly understood. In this work, we applied computational modeling to investigate the effects of macromolecular crowding on LLPS. To include biologically relevant LLPS dynamics, we extended the conventional Cahn–Hilliard model for phase separation by coupling it to experimentally derived macromolecular crowding dynamics and state-dependent reaction kinetics. Through extensive field-theoretic computer simulations, we show that the inclusion of macromolecular crowding results in late-stage coarsening and the stabilization of relatively smaller condensates. At a high crowding concentration, there is an accelerated growth and late-stage arrest of droplet formation, effectively resulting in anomalous labyrinthine morphologies akin to protein gelation observed in experiments. These results not only elucidate the crowder effects observed in experiments, but also highlight the importance of including state-dependent kinetics in LLPS models, and may help in designing further experiments to probe the intricate roles played by LLPS in self-organization dynamics of cells.https://www.mdpi.com/1422-0067/22/13/6675biomolecular condensatesmacromolecular crowdingmembraneless organellesliquid–liquid phase separationintrinsically disordered proteinsstate-dependent reactions |
| spellingShingle | Alick-O. Vweza Chul-Gyu Song Kil-To Chong Liquid–Liquid Phase Separation in the Presence of Macromolecular Crowding and State-dependent Kinetics International Journal of Molecular Sciences biomolecular condensates macromolecular crowding membraneless organelles liquid–liquid phase separation intrinsically disordered proteins state-dependent reactions |
| title | Liquid–Liquid Phase Separation in the Presence of Macromolecular Crowding and State-dependent Kinetics |
| title_full | Liquid–Liquid Phase Separation in the Presence of Macromolecular Crowding and State-dependent Kinetics |
| title_fullStr | Liquid–Liquid Phase Separation in the Presence of Macromolecular Crowding and State-dependent Kinetics |
| title_full_unstemmed | Liquid–Liquid Phase Separation in the Presence of Macromolecular Crowding and State-dependent Kinetics |
| title_short | Liquid–Liquid Phase Separation in the Presence of Macromolecular Crowding and State-dependent Kinetics |
| title_sort | liquid liquid phase separation in the presence of macromolecular crowding and state dependent kinetics |
| topic | biomolecular condensates macromolecular crowding membraneless organelles liquid–liquid phase separation intrinsically disordered proteins state-dependent reactions |
| url | https://www.mdpi.com/1422-0067/22/13/6675 |
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