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Binary peptide coacervates as an active model for biomolecular condensates

Author

Listed:
  • Shoupeng Cao

    (Sichuan University
    Max Planck Institute for Polymer Research)

  • Peng Zhou

    (Chinese Academy of Science)

  • Guizhi Shen

    (Chinese Academy of Science)

  • Tsvetomir Ivanov

    (Max Planck Institute for Polymer Research)

  • Xuehai Yan

    (Chinese Academy of Science)

  • Katharina Landfester

    (Max Planck Institute for Polymer Research)

  • Lucas Caire da Silva

    (Max Planck Institute for Polymer Research
    McGill University)

Abstract

Biomolecular condensates formed by proteins and nucleic acids are critical for cellular processes. Macromolecule-based coacervate droplets formed by liquid-liquid phase separation serve as synthetic analogues, but are limited by complex compositions and high molecular weights. Recently, short peptides have emerged as an alternative component of coacervates, but tend to form metastable microdroplets that evolve into rigid nanostructures. Here we present programmable coacervates using binary mixtures of diphenylalanine-based short peptides. We show that the presence of different short peptides stabilizes the coacervate phase and prevents the formation of rigid structures, allowing peptide coacervates to be used as stable adaptive compartments. This approach allows fine control of droplet formation and dynamic morphological changes in response to physiological triggers. As compartments, short peptide coacervates sequester hydrophobic molecules and enhance bio-orthogonal catalysis. In addition, the incorporation of coacervates into model synthetic cells enables the design of Boolean logic gates. Our findings highlight the potential of short peptide coacervates for creating adaptive biomimetic systems and provide insight into the principles of phase separation in biomolecular condensates.

Suggested Citation

  • Shoupeng Cao & Peng Zhou & Guizhi Shen & Tsvetomir Ivanov & Xuehai Yan & Katharina Landfester & Lucas Caire da Silva, 2025. "Binary peptide coacervates as an active model for biomolecular condensates," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57772-z
    DOI: 10.1038/s41467-025-57772-z
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    References listed on IDEAS

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    1. Yuri Hong & Saeed Najafi & Thomas Casey & Joan-Emma Shea & Song-I Han & Dong Soo Hwang, 2022. "Hydrophobicity of arginine leads to reentrant liquid-liquid phase separation behaviors of arginine-rich proteins," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Rachel S. Fisher & Shana Elbaum-Garfinkle, 2020. "Tunable multiphase dynamics of arginine and lysine liquid condensates," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    3. Wiggert J. Altenburg & N. Amy Yewdall & Daan F. M. Vervoort & Marleen H. M. E. Stevendaal & Alexander F. Mason & Jan C. M. Hest, 2020. "Programmed spatial organization of biomacromolecules into discrete, coacervate-based protocells," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    4. Jiahua Wang & Manzar Abbas & Junyou Wang & Evan Spruijt, 2023. "Selective amide bond formation in redox-active coacervate protocells," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    5. Can Xu & Nicolas Martin & Mei Li & Stephen Mann, 2022. "Living material assembly of bacteriogenic protocells," Nature, Nature, vol. 609(7929), pages 1029-1037, September.
    6. 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.
    7. Qi Guo & Guijin Zou & Xuliang Qian & Shujun Chen & Huajian Gao & Jing Yu, 2022. "Hydrogen-bonds mediate liquid-liquid phase separation of mussel derived adhesive peptides," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    8. Siddharth Deshpande & Frank Brandenburg & Anson Lau & Mart G. F. Last & Willem Kasper Spoelstra & Louis Reese & Sreekar Wunnava & Marileen Dogterom & Cees Dekker, 2019. "Spatiotemporal control of coacervate formation within liposomes," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    9. Fatma Pir Cakmak & Saehyun Choi & McCauley O. Meyer & Philip C. Bevilacqua & Christine D. Keating, 2020. "Prebiotically-relevant low polyion multivalency can improve functionality of membraneless compartments," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    10. Björn Drobot & Juan M. Iglesias-Artola & Kristian Vay & Viktoria Mayr & Mrityunjoy Kar & Moritz Kreysing & Hannes Mutschler & T-Y Dora Tang, 2018. "Compartmentalised RNA catalysis in membrane-free coacervate protocells," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
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