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Biomolecular condensates form spatially inhomogeneous network fluids

Author

Listed:
  • Furqan Dar

    (Washington University in St. Louis)

  • Samuel R. Cohen

    (Washington University in St. Louis
    Washington University in St. Louis)

  • Diana M. Mitrea

    (Dewpoint Therapeutics Inc.)

  • Aaron H. Phillips

    (St. Jude Children’s Research Hospital)

  • Gergely Nagy

    (Oak Ridge National Laboratory)

  • Wellington C. Leite

    (Oak Ridge National Laboratory)

  • Christopher B. Stanley

    (Oak Ridge National Laboratory)

  • Jeong-Mo Choi

    (Pusan National University)

  • Richard W. Kriwacki

    (St. Jude Children’s Research Hospital)

  • Rohit V. Pappu

    (Washington University in St. Louis)

Abstract

The functions of biomolecular condensates are thought to be influenced by their material properties, and these will be determined by the internal organization of molecules within condensates. However, structural characterizations of condensates are challenging, and rarely reported. Here, we deploy a combination of small angle neutron scattering, fluorescence recovery after photobleaching, and coarse-grained molecular dynamics simulations to provide structural descriptions of model condensates that are formed by macromolecules from nucleolar granular components (GCs). We show that these minimal facsimiles of GCs form condensates that are network fluids featuring spatial inhomogeneities across different length scales that reflect the contributions of distinct protein and peptide domains. The network-like inhomogeneous organization is characterized by a coexistence of liquid- and gas-like macromolecular densities that engenders bimodality of internal molecular dynamics. These insights suggest that condensates formed by multivalent proteins share features with network fluids formed by systems such as patchy or hairy colloids.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47602-z
    DOI: 10.1038/s41467-024-47602-z
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    1. 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.
    2. Wenqin Bai & Cameron J. Sargent & Jeong-Mo Choi & Rohit V. Pappu & Fuzhong Zhang, 2019. "Covalently-assembled single-chain protein nanostructures with ultra-high stability," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    3. Chenyang Lan & Juhyeong Kim & Svenja Ulferts & Fernando Aprile-Garcia & Sophie Weyrauch & Abhinaya Anandamurugan & Robert Grosse & Ritwick Sawarkar & Aleks Reinhardt & Thorsten Hugel, 2023. "Quantitative real-time in-cell imaging reveals heterogeneous clusters of proteins prior to condensation," Nature Communications, Nature, vol. 14(1), pages 1-8, 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. 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.
    6. 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.
    7. 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.
    8. 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.
    9. Diana M. Mitrea & Jaclyn A. Cika & Christopher B. Stanley & Amanda Nourse & Paulo L. Onuchic & Priya R. Banerjee & Aaron H. Phillips & Cheon-Gil Park & Ashok A. Deniz & Richard W. Kriwacki, 2018. "Self-interaction of NPM1 modulates multiple mechanisms of liquid–liquid phase separation," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    10. Khatcher O. Margossian & Marcel U. Brown & Todd Emrick & Murugappan Muthukumar, 2022. "Coacervation in polyzwitterion-polyelectrolyte systems and their potential applications for gastrointestinal drug delivery platforms," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    11. Pilong Li & Sudeep Banjade & Hui-Chun Cheng & Soyeon Kim & Baoyu Chen & Liang Guo & Marc Llaguno & Javoris V. Hollingsworth & David S. King & Salman F. Banani & Paul S. Russo & Qiu-Xing Jiang & B. Tra, 2012. "Phase transitions in the assembly of multivalent signalling proteins," Nature, Nature, vol. 483(7389), pages 336-340, March.
    12. Charles R. Harris & K. Jarrod Millman & Stéfan J. Walt & Ralf Gommers & Pauli Virtanen & David Cournapeau & Eric Wieser & Julian Taylor & Sebastian Berg & Nathaniel J. Smith & Robert Kern & Matti Picu, 2020. "Array programming with NumPy," Nature, Nature, vol. 585(7825), pages 357-362, September.
    13. Mylene C. Ferrolino & Diana M. Mitrea & J. Robert Michael & Richard W. Kriwacki, 2018. "Compositional adaptability in NPM1-SURF6 scaffolding networks enabled by dynamic switching of phase separation mechanisms," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
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