Microphase separation produces interfacial environment within diblock biomolecular condensates
The phase separation of intrinsically disordered proteins is emerging as an important mechanism for cellular organization. However, efforts to connect protein sequences to the physical properties of condensates, that is, the molecular grammar, are hampered by a lack of effective approaches for probi...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/90750 |
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| author | Andrew P Latham Longchen Zhu Dina A Sharon Songtao Ye Adam P Willard Xin Zhang Bin Zhang |
| author_facet | Andrew P Latham Longchen Zhu Dina A Sharon Songtao Ye Adam P Willard Xin Zhang Bin Zhang |
| author_sort | Andrew P Latham |
| collection | DOAJ |
| description | The phase separation of intrinsically disordered proteins is emerging as an important mechanism for cellular organization. However, efforts to connect protein sequences to the physical properties of condensates, that is, the molecular grammar, are hampered by a lack of effective approaches for probing high-resolution structural details. Using a combination of multiscale simulations and fluorescence lifetime imaging microscopy experiments, we systematically explored a series of systems consisting of diblock elastin-like polypeptides (ELPs). The simulations succeeded in reproducing the variation of condensate stability upon amino acid substitution and revealed different microenvironments within a single condensate, which we verified with environmentally sensitive fluorophores. The interspersion of hydrophilic and hydrophobic residues and a lack of secondary structure formation result in an interfacial environment, which explains both the strong correlation between ELP condensate stability and interfacial hydrophobicity scales, as well as the prevalence of protein-water hydrogen bonds. Our study uncovers new mechanisms for condensate stability and organization that may be broadly applicable. |
| format | Article |
| id | doaj-art-01b6eb5e652140c29c9883e3e5b9012d |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-01b6eb5e652140c29c9883e3e5b9012d2025-08-20T03:43:50ZengeLife Sciences Publications LtdeLife2050-084X2025-03-011210.7554/eLife.90750Microphase separation produces interfacial environment within diblock biomolecular condensatesAndrew P Latham0Longchen Zhu1Dina A Sharon2Songtao Ye3Adam P Willard4Xin Zhang5Bin Zhang6https://orcid.org/0000-0002-3685-7503Department of Chemistry, Massachusetts Institute of Technology, Cambridge, United StatesDepartment of Chemistry, School of Science and Research Center for Industries of the Future, Westlake University, Hangzhou, ChinaDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, United StatesDepartment of Chemistry, School of Science and Research Center for Industries of the Future, Westlake University, Hangzhou, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, ChinaDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, United StatesDepartment of Chemistry, School of Science and Research Center for Industries of the Future, Westlake University, Hangzhou, ChinaDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, United StatesThe phase separation of intrinsically disordered proteins is emerging as an important mechanism for cellular organization. However, efforts to connect protein sequences to the physical properties of condensates, that is, the molecular grammar, are hampered by a lack of effective approaches for probing high-resolution structural details. Using a combination of multiscale simulations and fluorescence lifetime imaging microscopy experiments, we systematically explored a series of systems consisting of diblock elastin-like polypeptides (ELPs). The simulations succeeded in reproducing the variation of condensate stability upon amino acid substitution and revealed different microenvironments within a single condensate, which we verified with environmentally sensitive fluorophores. The interspersion of hydrophilic and hydrophobic residues and a lack of secondary structure formation result in an interfacial environment, which explains both the strong correlation between ELP condensate stability and interfacial hydrophobicity scales, as well as the prevalence of protein-water hydrogen bonds. Our study uncovers new mechanisms for condensate stability and organization that may be broadly applicable.https://elifesciences.org/articles/90750biomolecular condensatesmolecular dynamicsmultiscale simulationshydrophobicity |
| spellingShingle | Andrew P Latham Longchen Zhu Dina A Sharon Songtao Ye Adam P Willard Xin Zhang Bin Zhang Microphase separation produces interfacial environment within diblock biomolecular condensates eLife biomolecular condensates molecular dynamics multiscale simulations hydrophobicity |
| title | Microphase separation produces interfacial environment within diblock biomolecular condensates |
| title_full | Microphase separation produces interfacial environment within diblock biomolecular condensates |
| title_fullStr | Microphase separation produces interfacial environment within diblock biomolecular condensates |
| title_full_unstemmed | Microphase separation produces interfacial environment within diblock biomolecular condensates |
| title_short | Microphase separation produces interfacial environment within diblock biomolecular condensates |
| title_sort | microphase separation produces interfacial environment within diblock biomolecular condensates |
| topic | biomolecular condensates molecular dynamics multiscale simulations hydrophobicity |
| url | https://elifesciences.org/articles/90750 |
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