Multiphasic condensates formed with mono-component of tetrapeptides via phase separation

Abstract Biomolecular condensates, formed by liquid-liquid phase separation of biomacromolecules, play crucial roles in regulating physiological events in biological systems. While multiphasic condensates have been extensively studied, those derived from a single component of short peptides have not...

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Main Authors: Laicheng Zhou, Longchen Zhu, Cong Wang, Tengyan Xu, Jing Wang, Bin Zhang, Xin Zhang, Huaimin Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58060-6
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author Laicheng Zhou
Longchen Zhu
Cong Wang
Tengyan Xu
Jing Wang
Bin Zhang
Xin Zhang
Huaimin Wang
author_facet Laicheng Zhou
Longchen Zhu
Cong Wang
Tengyan Xu
Jing Wang
Bin Zhang
Xin Zhang
Huaimin Wang
author_sort Laicheng Zhou
collection DOAJ
description Abstract Biomolecular condensates, formed by liquid-liquid phase separation of biomacromolecules, play crucial roles in regulating physiological events in biological systems. While multiphasic condensates have been extensively studied, those derived from a single component of short peptides have not yet been reported. Here, we report the symmetrical core-shell structural biomolecular condensates formed with a programmable tetrapeptide library via phase separation. Our findings reveal that tryptophan is essential for core-shell structure formation due to its strongest homotypical π-π interaction, enabling us to modulate the structure of condensates from core-shell to homogeneous by altering the amino acid composition. Molecular dynamics simulation combined with cryogenic focused ion beam scanning electron microscopy and cryogenic electron microscopy show that the inner core of multiphasic tetrapeptide condensates is solid-like, consisting of ordered structures. The core is enveloped by a liquid-like shell, stabilizing the core structure. Furthermore, we demonstrate control over multiphasic condensate formation through intrinsic redox reactions or post-translational modifications, facilitating the rational design of synthetic multiphasic condensates for various applications on demand.
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spelling doaj-art-432317a580d64edf918cc306cac9efda2025-08-20T03:41:49ZengNature PortfolioNature Communications2041-17232025-03-0116111410.1038/s41467-025-58060-6Multiphasic condensates formed with mono-component of tetrapeptides via phase separationLaicheng Zhou0Longchen Zhu1Cong Wang2Tengyan Xu3Jing Wang4Bin Zhang5Xin Zhang6Huaimin Wang7Department of Chemistry, Zhejiang UniversityDepartment of Chemistry, School of Science, Westlake UniversityDepartment of Chemistry, Massachusetts Institute of TechnologyDepartment of Chemistry, School of Science, Westlake UniversityDepartment of Chemistry, School of Science, Westlake UniversityDepartment of Chemistry, Massachusetts Institute of TechnologyDepartment of Chemistry, School of Science, Westlake UniversityDepartment of Chemistry, School of Science, Westlake UniversityAbstract Biomolecular condensates, formed by liquid-liquid phase separation of biomacromolecules, play crucial roles in regulating physiological events in biological systems. While multiphasic condensates have been extensively studied, those derived from a single component of short peptides have not yet been reported. Here, we report the symmetrical core-shell structural biomolecular condensates formed with a programmable tetrapeptide library via phase separation. Our findings reveal that tryptophan is essential for core-shell structure formation due to its strongest homotypical π-π interaction, enabling us to modulate the structure of condensates from core-shell to homogeneous by altering the amino acid composition. Molecular dynamics simulation combined with cryogenic focused ion beam scanning electron microscopy and cryogenic electron microscopy show that the inner core of multiphasic tetrapeptide condensates is solid-like, consisting of ordered structures. The core is enveloped by a liquid-like shell, stabilizing the core structure. Furthermore, we demonstrate control over multiphasic condensate formation through intrinsic redox reactions or post-translational modifications, facilitating the rational design of synthetic multiphasic condensates for various applications on demand.https://doi.org/10.1038/s41467-025-58060-6
spellingShingle Laicheng Zhou
Longchen Zhu
Cong Wang
Tengyan Xu
Jing Wang
Bin Zhang
Xin Zhang
Huaimin Wang
Multiphasic condensates formed with mono-component of tetrapeptides via phase separation
Nature Communications
title Multiphasic condensates formed with mono-component of tetrapeptides via phase separation
title_full Multiphasic condensates formed with mono-component of tetrapeptides via phase separation
title_fullStr Multiphasic condensates formed with mono-component of tetrapeptides via phase separation
title_full_unstemmed Multiphasic condensates formed with mono-component of tetrapeptides via phase separation
title_short Multiphasic condensates formed with mono-component of tetrapeptides via phase separation
title_sort multiphasic condensates formed with mono component of tetrapeptides via phase separation
url https://doi.org/10.1038/s41467-025-58060-6
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