IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-58900-5.html
   My bibliography  Save this article

Controlled and orthogonal partitioning of large particles into biomolecular condensates

Author

Listed:
  • Fleurie M. Kelley

    (Rutgers, The State University of New Jersey)

  • Anas Ani

    (Rutgers, The State University of New Jersey
    Rutgers, The State University of New Jersey)

  • Emily G. Pinlac

    (Rutgers, The State University of New Jersey)

  • Bridget Linders

    (Rutgers, The State University of New Jersey)

  • Bruna Favetta

    (Rutgers, The State University of New Jersey)

  • Mayur Barai

    (Rutgers, The State University of New Jersey)

  • Yuchen Ma

    (Rutgers, The State University of New Jersey)

  • Arjun Singh

    (Rutgers, The State University of New Jersey)

  • Gregory L. Dignon

    (Rutgers, The State University of New Jersey)

  • Yuwei Gu

    (Rutgers, The State University of New Jersey)

  • Benjamin S. Schuster

    (Rutgers, The State University of New Jersey)

Abstract

Partitioning of client molecules into biomolecular condensates is critical for regulating the composition and function of condensates. Previous studies suggest that client size limits partitioning. Here, we ask whether large clients, such as macromolecular complexes and nanoparticles, can partition into condensates based on particle-condensate interactions. We seek to discover the fundamental biophysical principles that govern particle inclusion in or exclusion from condensates, using polymer nanoparticles surface-functionalized with biotin or oligonucleotides. Based on our experiments, coarse-grained molecular dynamics simulations, and theory, we conclude that arbitrarily large particles can controllably partition into condensates given sufficiently strong condensate-particle interactions. Remarkably, we also observe that beads with distinct surface chemistries partition orthogonally into immiscible condensates. These findings may provide insights into how various cellular processes are achieved based on partitioning of large clients into biomolecular condensates, and they offer design principles for drug delivery systems that selectively target disease-related condensates.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58900-5
    DOI: 10.1038/s41467-025-58900-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-58900-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-58900-5?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. Benjamin S. Schuster & Ellen H. Reed & Ranganath Parthasarathy & Craig N. Jahnke & Reese M. Caldwell & Jessica G. Bermudez & Holly Ramage & Matthew C. Good & Daniel A. Hammer, 2018. "Controllable protein phase separation and modular recruitment to form responsive membraneless organelles," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Liran Fu & Erika N. Weiskopf & Onno Akkermans & Nicholas A. Swanson & Shiya Cheng & Thomas U. Schwartz & Dirk Görlich, 2024. "HIV-1 capsids enter the FG phase of nuclear pores like a transport receptor," Nature, Nature, vol. 626(8000), pages 843-851, February.
    3. Anamika Avni & Ashish Joshi & Anuja Walimbe & Swastik G. Pattanashetty & Samrat Mukhopadhyay, 2022. "Single-droplet surface-enhanced Raman scattering decodes the molecular determinants of liquid-liquid phase separation," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. 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.
    5. Joshua A. Riback & Lian Zhu & Mylene C. Ferrolino & Michele Tolbert & Diana M. Mitrea & David W. Sanders & Ming-Tzo Wei & Richard W. Kriwacki & Clifford P. Brangwynne, 2020. "Composition-dependent thermodynamics of intracellular phase separation," Nature, Nature, vol. 581(7807), pages 209-214, May.
    6. Yang Eric Guo & John C. Manteiga & Jonathan E. Henninger & Benjamin R. Sabari & Alessandra Dall’Agnese & Nancy M. Hannett & Jan-Hendrik Spille & Lena K. Afeyan & Alicia V. Zamudio & Krishna Shrinivas , 2019. "Pol II phosphorylation regulates a switch between transcriptional and splicing condensates," Nature, Nature, vol. 572(7770), pages 543-548, August.
    7. Adriana Savastano & Alain Ibáñez de Opakua & Marija Rankovic & Markus Zweckstetter, 2020. "Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Simon Alberti & Paolo Arosio & Robert B. Best & Steven Boeynaems & Danfeng Cai & Rosana Collepardo-Guevara & Gregory L. Dignon & Rumiana Dimova & Shana Elbaum-Garfinkle & Nicolas L. Fawzi & Monika Fux, 2025. "Current practices in the study of biomolecular condensates: a community comment," Nature Communications, Nature, vol. 16(1), pages 1-14, December.

    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. Simon Alberti & Paolo Arosio & Robert B. Best & Steven Boeynaems & Danfeng Cai & Rosana Collepardo-Guevara & Gregory L. Dignon & Rumiana Dimova & Shana Elbaum-Garfinkle & Nicolas L. Fawzi & Monika Fux, 2025. "Current practices in the study of biomolecular condensates: a community comment," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    2. 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.
    3. Halima H. Schede & Pradeep Natarajan & Arup K. Chakraborty & Krishna Shrinivas, 2023. "A model for organization and regulation of nuclear condensates by gene activity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Ashish Joshi & Anuja Walimbe & Anamika Avni & Sandeep K. Rai & Lisha Arora & Snehasis Sarkar & Samrat Mukhopadhyay, 2023. "Single-molecule FRET unmasks structural subpopulations and crucial molecular events during FUS low-complexity domain phase separation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. 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.
    6. Mina Farag & Wade M. Borcherds & Anne Bremer & Tanja Mittag & Rohit V. Pappu, 2023. "Phase separation of protein mixtures is driven by the interplay of homotypic and heterotypic interactions," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    7. Ellen H. Brumbaugh-Reed & Yang Gao & Kazuhiro Aoki & Jared E. Toettcher, 2024. "Rapid and reversible dissolution of biomolecular condensates using light-controlled recruitment of a solubility tag," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    8. Yan Huang & Haixu Chen & Xin Qiao & Shangsong Li & Xiaoliang Wang & Xiaoman Liu & Xin Huang, 2025. "Liquid-liquid phase separation-boosted transmembrane delivery in interactive protocell communities," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    9. 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.
    10. 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.
    11. Aishwarya Agarwal & Lisha Arora & Sandeep K. Rai & Anamika Avni & Samrat Mukhopadhyay, 2022. "Spatiotemporal modulations in heterotypic condensates of prion and α-synuclein control phase transitions and amyloid conversion," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    12. Baolei Yuan & Xuan Zhou & Keiichiro Suzuki & Gerardo Ramos-Mandujano & Mengge Wang & Muhammad Tehseen & Lorena V. Cortés-Medina & James J. Moresco & Sarah Dunn & Reyna Hernandez-Benitez & Tomoaki Hish, 2022. "Wiskott-Aldrich syndrome protein forms nuclear condensates and regulates alternative splicing," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    13. Jiang Ren & Shuai Wang & Zhi Zong & Ting Pan & Sijia Liu & Wei Mao & Huizhe Huang & Xiaohua Yan & Bing Yang & Xin He & Fangfang Zhou & Long Zhang, 2024. "TRIM28-mediated nucleocapsid protein SUMOylation enhances SARS-CoV-2 virulence," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    14. Akiko Doi & Gianmarco D. Suarez & Rita Droste & H. Robert Horvitz, 2023. "A DEAD-box helicase drives the partitioning of a pro-differentiation NAB protein into nuclear foci," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    15. Mark F. Nüesch & Lisa Pietrek & Erik D. Holmstrom & Daniel Nettels & Valentin Roten & Rafael Kronenberg-Tenga & Ohad Medalia & Gerhard Hummer & Benjamin Schuler, 2024. "Nanosecond chain dynamics of single-stranded nucleic acids," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    16. Mirren Charnley & Saba Islam & Guneet K. Bindra & Jeremy Engwirda & Julian Ratcliffe & Jiangtao Zhou & Raffaele Mezzenga & Mark D. Hulett & Kyunghoon Han & Joshua T. Berryman & Nicholas P. Reynolds, 2022. "Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    17. Hossein Salari & Geneviève Fourel & Daniel Jost, 2024. "Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    18. 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.
    19. Jorine M. Eeftens & Manya Kapoor & Davide Michieletto & Clifford P. Brangwynne, 2021. "Polycomb condensates can promote epigenetic marks but are not required for sustained chromatin compaction," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    20. Emily L. Spaulding & Alexis M. Feidler & Lio A. Cook & Dustin L. Updike, 2022. "RG/RGG repeats in the C. elegans homologs of Nucleolin and GAR1 contribute to sub-nucleolar phase separation," 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:16:y:2025:i:1:d:10.1038_s41467-025-58900-5. 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.