IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46223-w.html
   My bibliography  Save this article

Sequence-dependent material properties of biomolecular condensates and their relation to dilute phase conformations

Author

Listed:
  • Dinesh Sundaravadivelu Devarajan

    (Texas A&M University)

  • Jiahui Wang

    (Texas A&M University)

  • Beata Szała-Mendyk

    (Texas A&M University)

  • Shiv Rekhi

    (Texas A&M University)

  • Arash Nikoubashman

    (Leibniz-Institut für Polymerforschung Dresden e.V.
    Technische Universität Dresden
    Technische Universität Dresden)

  • Young C. Kim

    (Naval Research Laboratory)

  • Jeetain Mittal

    (Texas A&M University
    Texas A&M University
    Texas A&M University)

Abstract

Material properties of phase-separated biomolecular condensates, enriched with disordered proteins, dictate many cellular functions. Contrary to the progress made in understanding the sequence-dependent phase separation of proteins, little is known about the sequence determinants of condensate material properties. Using the hydropathy scale and Martini models, we computationally decipher these relationships for charge-rich disordered protein condensates. Our computations yield dynamical, rheological, and interfacial properties of condensates that are quantitatively comparable with experimentally characterized condensates. Interestingly, we find that the material properties of model and natural proteins respond similarly to charge segregation, despite different sequence compositions. Molecular interactions within the condensates closely resemble those within the single-chain ensembles. Consequently, the material properties strongly correlate with molecular contact dynamics and single-chain structural properties. We demonstrate the potential to harness the sequence characteristics of disordered proteins for predicting and engineering the material properties of functional condensates, with insights from the dilute phase properties.

Suggested Citation

  • Dinesh Sundaravadivelu Devarajan & Jiahui Wang & Beata Szała-Mendyk & Shiv Rekhi & Arash Nikoubashman & Young C. Kim & Jeetain Mittal, 2024. "Sequence-dependent material properties of biomolecular condensates and their relation to dilute phase conformations," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46223-w
    DOI: 10.1038/s41467-024-46223-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46223-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-46223-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Keren Lasker & Steven Boeynaems & Vinson Lam & Daniel Scholl & Emma Stainton & Adam Briner & Maarten Jacquemyn & Dirk Daelemans & Ashok Deniz & Elizabeth Villa & Alex S. Holehouse & Aaron D. Gitler & , 2022. "The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems," 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. Archishman Ghosh & Divya Kota & Huan-Xiang Zhou, 2021. "Shear relaxation governs fusion dynamics of biomolecular condensates," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    4. Ibraheem Alshareedah & Mahdi Muhammad Moosa & Matthew Pham & Davit A. Potoyan & Priya R. Banerjee, 2021. "Programmable viscoelasticity in protein-RNA condensates with disordered sticker-spacer polypeptides," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    5. Andres R. Tejedor & Ignacio Sanchez-Burgos & Maria Estevez-Espinosa & Adiran Garaizar & Rosana Collepardo-Guevara & Jorge Ramirez & Jorge R. Espinosa, 2022. "Protein structural transitions critically transform the network connectivity and viscoelasticity of RNA-binding protein condensates but RNA can prevent it," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Nicola Galvanetto & Miloš T. Ivanović & Aritra Chowdhury & Andrea Sottini & Mark F. Nüesch & Daniel Nettels & Robert B. Best & Benjamin Schuler, 2023. "Extreme dynamics in a biomolecular condensate," Nature, Nature, vol. 619(7971), pages 876-883, July.
    7. Jaime Agudo-Canalejo & Sebastian W. Schultz & Haruka Chino & Simona M. Migliano & Chieko Saito & Ikuko Koyama-Honda & Harald Stenmark & Andreas Brech & Alexander I. May & Noboru Mizushima & Roland L. , 2021. "Wetting regulates autophagy of phase-separated compartments and the cytosol," Nature, Nature, vol. 591(7848), pages 142-146, March.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Furqan Dar & Samuel R. Cohen & Diana M. Mitrea & Aaron H. Phillips & Gergely Nagy & Wellington C. Leite & Christopher B. Stanley & Jeong-Mo Choi & Richard W. Kriwacki & Rohit V. Pappu, 2024. "Biomolecular condensates form spatially inhomogeneous network fluids," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Min Lee & Hyungseok C. Moon & Hyeonjeong Jeong & Dong Wook Kim & Hye Yoon Park & Yongdae Shin, 2024. "Optogenetic control of mRNA condensation reveals an intimate link between condensate material properties and functions," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Miriam Linsenmeier & Maria Hondele & Fulvio Grigolato & Eleonora Secchi & Karsten Weis & Paolo Arosio, 2022. "Dynamic arrest and aging of biomolecular condensates are modulated by low-complexity domains, RNA and biochemical activity," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. Agustín Mangiarotti & Macarena Siri & Nicky W. Tam & Ziliang Zhao & Leonel Malacrida & Rumiana Dimova, 2023. "Biomolecular condensates modulate membrane lipid packing and hydration," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Viet Sang Doan & Ibraheem Alshareedah & Anurag Singh & Priya R. Banerjee & Sangwoo Shin, 2024. "Diffusiophoresis promotes phase separation and transport of biomolecular condensates," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    6. Saumyak Mukherjee & Lars V. Schäfer, 2023. "Thermodynamic forces from protein and water govern condensate formation of an intrinsically disordered protein domain," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    7. Ibraheem Alshareedah & Mahdi Muhammad Moosa & Matthew Pham & Davit A. Potoyan & Priya R. Banerjee, 2021. "Programmable viscoelasticity in protein-RNA condensates with disordered sticker-spacer polypeptides," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    8. Mark D. Driver & Patrick R. Onck, 2025. "Selective phase separation of transcription factors is driven by orthogonal molecular grammar," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    9. Emanuele Zippo & Dorothee Dormann & Thomas Speck & Lukas S. Stelzl, 2025. "Molecular simulations of enzymatic phosphorylation of disordered proteins and their condensates," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    10. Andrew Z. Lin & Kiersten M. Ruff & Furqan Dar & Ameya Jalihal & Matthew R. King & Jared M. Lalmansingh & Ammon E. Posey & Nadia A. Erkamp & Ian Seim & Amy S. Gladfelter & Rohit V. Pappu, 2023. "Dynamical control enables the formation of demixed biomolecular condensates," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. 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.
    12. Giuseppe Sicoli & Daniel Sieme & Kerstin Overkamp & Mahdi Khalil & Robin Backer & Christian Griesinger & Dieter Willbold & Nasrollah Rezaei-Ghaleh, 2024. "Large dynamics of a phase separating arginine-glycine-rich domain revealed via nuclear and electron spins," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    13. Thomas Litschel & Charlotte F. Kelley & Xiaohang Cheng & Leon Babl & Naoko Mizuno & Lindsay B. Case & Petra Schwille, 2024. "Membrane-induced 2D phase separation of the focal adhesion protein talin," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    14. Y Hoang & Christopher A. Azaldegui & Rachel E. Dow & Maria Ghalmi & Julie S. Biteen & Anthony G. Vecchiarelli, 2024. "An experimental framework to assess biomolecular condensates in bacteria," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    15. Rosa Antón & Miguel Á. Treviño & David Pantoja-Uceda & Sara Félix & María Babu & Eurico J. Cabrita & Markus Zweckstetter & Philip Tinnefeld & Andrés M. Vera & Javier Oroz, 2024. "Alternative low-populated conformations prompt phase transitions in polyalanine repeat expansions," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    16. 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.
    17. Wenwen Yu & Ke Jin & Dandan Wang & Nankai Wang & Yangyang Li & Yanfeng Liu & Jianghua Li & Guocheng Du & Xueqin Lv & Jian Chen & Rodrigo Ledesma-Amaro & Long Liu, 2024. "De novo engineering of programmable and multi-functional biomolecular condensates for controlled biosynthesis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    18. Fleurie M. Kelley & Anas Ani & Emily G. Pinlac & Bridget Linders & Bruna Favetta & Mayur Barai & Yuchen Ma & Arjun Singh & Gregory L. Dignon & Yuwei Gu & Benjamin S. Schuster, 2025. "Controlled and orthogonal partitioning of large particles into biomolecular condensates," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    19. David Q. P. Reis & Sara Pereira & Ana P. Ramos & Pedro M. Pereira & Leonor Morgado & Joana Calvário & Adriano O. Henriques & Mónica Serrano & Ana S. Pina, 2024. "Catalytic peptide-based coacervates for enhanced function through structural organization and substrate specificity," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    20. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46223-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.