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

Author

Listed:
  • Laicheng Zhou

    (Zhejiang University
    Westlake University
    Westlake Institute for Advanced Study)

  • Longchen Zhu

    (Westlake University
    Westlake Institute for Advanced Study)

  • Cong Wang

    (Massachusetts Institute of Technology)

  • Tengyan Xu

    (Westlake University
    Westlake Institute for Advanced Study)

  • Jing Wang

    (Westlake University
    Westlake Institute for Advanced Study)

  • Bin Zhang

    (Massachusetts Institute of Technology)

  • Xin Zhang

    (Westlake University
    Westlake Institute for Advanced Study
    Westlake University)

  • Huaimin Wang

    (Westlake University
    Westlake Institute for Advanced Study
    Westlake University)

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.

Suggested Citation

  • Laicheng Zhou & Longchen Zhu & Cong Wang & Tengyan Xu & Jing Wang & Bin Zhang & Xin Zhang & Huaimin Wang, 2025. "Multiphasic condensates formed with mono-component of tetrapeptides via phase separation," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58060-6
    DOI: 10.1038/s41467-025-58060-6
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    References listed on IDEAS

    as
    1. Tengyan Xu & Jiaqi Wang & Shuang Zhao & Dinghao Chen & Hongyue Zhang & Yu Fang & Nan Kong & Ziao Zhou & Wenbin Li & Huaimin Wang, 2023. "Accelerating the prediction and discovery of peptide hydrogels with human-in-the-loop," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Bartosz Gabryelczyk & Hao Cai & Xiangyan Shi & Yue Sun & Piet J. M. Swinkels & Stefan Salentinig & Konstantin Pervushin & Ali Miserez, 2019. "Hydrogen bond guidance and aromatic stacking drive liquid-liquid phase separation of intrinsically disordered histidine-rich peptides," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    3. Avigail Baruch Leshem & Sian Sloan-Dennison & Tlalit Massarano & Shavit Ben-David & Duncan Graham & Karen Faulds & Hugo E. Gottlieb & Jordan H. Chill & Ayala Lampel, 2023. "Biomolecular condensates formed by designer minimalistic peptides," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    4. Taranpreet Kaur & Muralikrishna Raju & Ibraheem Alshareedah & Richoo B. Davis & Davit A. Potoyan & Priya R. Banerjee, 2021. "Sequence-encoded and composition-dependent protein-RNA interactions control multiphasic condensate morphologies," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
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