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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
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