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Dynamic control of DNA condensation

Author

Listed:
  • Siddharth Agarwal

    (University of California at Los Angeles
    University of California at Los Angeles)

  • Dino Osmanovic

    (University of California at Los Angeles)

  • Mahdi Dizani

    (University of California at Los Angeles)

  • Melissa A. Klocke

    (University of California at Los Angeles)

  • Elisa Franco

    (University of California at Los Angeles
    University of California at Los Angeles)

Abstract

Artificial biomolecular condensates are emerging as a versatile approach to organize molecular targets and reactions without the need for lipid membranes. Here we ask whether the temporal response of artificial condensates can be controlled via designed chemical reactions. We address this general question by considering a model problem in which a phase separating component participates in reactions that dynamically activate or deactivate its ability to self-attract. Through a theoretical model we illustrate the transient and equilibrium effects of reactions, linking condensate response and reaction parameters. We experimentally realize our model problem using star-shaped DNA motifs known as nanostars to generate condensates, and we take advantage of strand invasion and displacement reactions to kinetically control the capacity of nanostars to interact. We demonstrate reversible dissolution and growth of DNA condensates in the presence of specific DNA inputs, and we characterize the role of toehold domains, nanostar size, and nanostar valency. Our results will support the development of artificial biomolecular condensates that can adapt to environmental changes with prescribed temporal dynamics.

Suggested Citation

  • Siddharth Agarwal & Dino Osmanovic & Mahdi Dizani & Melissa A. Klocke & Elisa Franco, 2024. "Dynamic control of DNA condensation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46266-z
    DOI: 10.1038/s41467-024-46266-z
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    References listed on IDEAS

    as
    1. Siddharth Agarwal & Melissa A. Klocke & Passa E. Pungchai & Elisa Franco, 2021. "Dynamic self-assembly of compartmentalized DNA nanotubes," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Samuel W. Schaffter & Dominic Scalise & Terence M. Murphy & Anusha Patel & Rebecca Schulman, 2020. "Feedback regulation of crystal growth by buffering monomer concentration," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    3. Philip Petersen & Grigory Tikhomirov & Lulu Qian, 2018. "Information-based autonomous reconfiguration in systems of interacting DNA nanostructures," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    4. Ankur Jain & Ronald D. Vale, 2017. "RNA phase transitions in repeat expansion disorders," Nature, Nature, vol. 546(7657), pages 243-247, June.
    5. Liang Yue & Shan Wang & Verena Wulf & Itamar Willner, 2019. "Stiffness-switchable DNA-based constitutional dynamic network hydrogels for self-healing and matrix-guided controlled chemical processes," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    6. Paul W K Rothemund & Nick Papadakis & Erik Winfree, 2004. "Algorithmic Self-Assembly of DNA Sierpinski Triangles," PLOS Biology, Public Library of Science, vol. 2(12), pages 1-1, December.
    7. Joshua Fern & Rebecca Schulman, 2018. "Modular DNA strand-displacement controllers for directing material expansion," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
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