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Liquid-liquid phase separation-boosted transmembrane delivery in interactive protocell communities

Author

Listed:
  • Yan Huang

    (Harbin Institute of Technology)

  • Haixu Chen

    (Harbin Institute of Technology)

  • Xin Qiao

    (Harbin Institute of Technology)

  • Shangsong Li

    (Harbin Institute of Technology)

  • Xiaoliang Wang

    (Harbin Institute of Technology)

  • Xiaoman Liu

    (Harbin Institute of Technology)

  • Xin Huang

    (Harbin Institute of Technology)

Abstract

Stress stimulation-mediated liquid-liquid phase separation is a key activity in living organisms, but its biophysical characteristics are poorly understood. Here, we report a UV-light stress stimulation behaviour in a binary community of synthetic protocells of condensates and proteinosomes, showing that condensates could behave like Condensate Pumps to enable a stepwise controlled transmembrane mass transfer regardless of the permeability barrier of proteinosomes. The stimulation mechanism of interfacial tension-induced proteinosome deformation and transient high osmotic pressure arisen by the dissociation of condensate is proposed. Accordingly, under UV-light stress stimulation, unexpected characteristics could be triggered by transmembrane pumping oversized biomacromolecules into proteinosomes including liquid-liquid reentrant phase separation, DNA unwinding, and protein synthesis. Therefore, our results not only reveal unique physical principles and potential characteristics of macromolecular assemblies at droplet-membrane interface but also highlight a pathway for transmembrane transport of biomacromolecules which is anticipated to serve as a powerful technique to inducing higher-order behaviour in synthetic protocells community.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60541-7
    DOI: 10.1038/s41467-025-60541-7
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    1. Adam G. Larson & Daniel Elnatan & Madeline M. Keenen & Michael J. Trnka & Jonathan B. Johnston & Alma L. Burlingame & David A. Agard & Sy Redding & Geeta J. Narlikar, 2017. "Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin," Nature, Nature, vol. 547(7662), pages 236-240, July.
    2. 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.
    3. Xin Huang & Mei Li & David C. Green & David S. Williams & Avinash J. Patil & Stephen Mann, 2013. "Interfacial assembly of protein–polymer nano-conjugates into stimulus-responsive biomimetic protocells," Nature Communications, Nature, vol. 4(1), pages 1-9, October.
    4. 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.
    5. Lei Zhang & Xinran Geng & Fangfang Wang & Jinshan Tang & Yu Ichida & Arishya Sharma & Sora Jin & Mingyue Chen & Mingliang Tang & Franklin Mayca Pozo & Wenxiu Wang & Janet Wang & Michal Wozniak & Xiaox, 2022. "Author Correction: 53BP1 regulates heterochromatin through liquid phase separation," Nature Communications, Nature, vol. 13(1), pages 1-1, December.
    6. Lei Zhang & Xinran Geng & Fangfang Wang & Jinshan Tang & Yu Ichida & Arishya Sharma & Sora Jin & Mingyue Chen & Mingliang Tang & Franklin Mayca Pozo & Wenxiu Wang & Janet Wang & Michal Wozniak & Xiaox, 2022. "53BP1 regulates heterochromatin through liquid phase separation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Bernardo Gouveia & Yoonji Kim & Joshua W. Shaevitz & Sabine Petry & Howard A. Stone & Clifford P. Brangwynne, 2022. "Capillary forces generated by biomolecular condensates," Nature, Nature, vol. 609(7926), pages 255-264, September.
    8. Taranpreet Kaur & Muralikrishna Raju & Ibraheem Alshareedah & Richoo B. Davis & Davit A. Potoyan & Priya R. Banerjee, 2021. "Sequence-encoded and composition-dependent protein-RNA interactions control multiphasic condensate morphologies," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    9. Amy R. Strom & Alexander V. Emelyanov & Mustafa Mir & Dmitry V. Fyodorov & Xavier Darzacq & Gary H. Karpen, 2017. "Phase separation drives heterochromatin domain formation," Nature, Nature, vol. 547(7662), pages 241-245, July.
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