Liquid–Liquid Phase Separation in Crowded Environments
Biomolecular condensates play a key role in organizing cellular fluids such as the cytoplasm and nucleoplasm. Most of these non-membranous organelles show liquid-like properties both in cells and when studied in vitro through liquid–liquid phase separation (LLPS) of purified proteins. In general, LL...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/16/5908 |
| _version_ | 1797557500148449280 |
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| author | Alain A. M. André Evan Spruijt |
| author_facet | Alain A. M. André Evan Spruijt |
| author_sort | Alain A. M. André |
| collection | DOAJ |
| description | Biomolecular condensates play a key role in organizing cellular fluids such as the cytoplasm and nucleoplasm. Most of these non-membranous organelles show liquid-like properties both in cells and when studied in vitro through liquid–liquid phase separation (LLPS) of purified proteins. In general, LLPS of proteins is known to be sensitive to variations in pH, temperature and ionic strength, but the role of crowding remains underappreciated. Several decades of research have shown that macromolecular crowding can have profound effects on protein interactions, folding and aggregation, and it must, by extension, also impact LLPS. However, the precise role of crowding in LLPS is far from trivial, as most condensate components have a disordered nature and exhibit multiple weak attractive interactions. Here, we discuss which factors determine the scope of LLPS in crowded environments, and we review the evidence for the impact of macromolecular crowding on phase boundaries, partitioning behavior and condensate properties. Based on a comparison of both in vivo and in vitro LLPS studies, we propose that phase separation in cells does not solely rely on attractive interactions, but shows important similarities to segregative phase separation. |
| first_indexed | 2024-03-10T17:17:46Z |
| format | Article |
| id | doaj.art-fa209d543bd3467d8b10a315173719ef |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T17:17:46Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fa209d543bd3467d8b10a315173719ef2023-11-20T10:26:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012116590810.3390/ijms21165908Liquid–Liquid Phase Separation in Crowded EnvironmentsAlain A. M. André0Evan Spruijt1Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The NetherlandsInstitute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The NetherlandsBiomolecular condensates play a key role in organizing cellular fluids such as the cytoplasm and nucleoplasm. Most of these non-membranous organelles show liquid-like properties both in cells and when studied in vitro through liquid–liquid phase separation (LLPS) of purified proteins. In general, LLPS of proteins is known to be sensitive to variations in pH, temperature and ionic strength, but the role of crowding remains underappreciated. Several decades of research have shown that macromolecular crowding can have profound effects on protein interactions, folding and aggregation, and it must, by extension, also impact LLPS. However, the precise role of crowding in LLPS is far from trivial, as most condensate components have a disordered nature and exhibit multiple weak attractive interactions. Here, we discuss which factors determine the scope of LLPS in crowded environments, and we review the evidence for the impact of macromolecular crowding on phase boundaries, partitioning behavior and condensate properties. Based on a comparison of both in vivo and in vitro LLPS studies, we propose that phase separation in cells does not solely rely on attractive interactions, but shows important similarities to segregative phase separation.https://www.mdpi.com/1422-0067/21/16/5908liquid–liquid phase separationintrinsically disordered proteinscrowdingmembraneless organelles |
| spellingShingle | Alain A. M. André Evan Spruijt Liquid–Liquid Phase Separation in Crowded Environments International Journal of Molecular Sciences liquid–liquid phase separation intrinsically disordered proteins crowding membraneless organelles |
| title | Liquid–Liquid Phase Separation in Crowded Environments |
| title_full | Liquid–Liquid Phase Separation in Crowded Environments |
| title_fullStr | Liquid–Liquid Phase Separation in Crowded Environments |
| title_full_unstemmed | Liquid–Liquid Phase Separation in Crowded Environments |
| title_short | Liquid–Liquid Phase Separation in Crowded Environments |
| title_sort | liquid liquid phase separation in crowded environments |
| topic | liquid–liquid phase separation intrinsically disordered proteins crowding membraneless organelles |
| url | https://www.mdpi.com/1422-0067/21/16/5908 |
| work_keys_str_mv | AT alainamandre liquidliquidphaseseparationincrowdedenvironments AT evanspruijt liquidliquidphaseseparationincrowdedenvironments |