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Lipid packing and cholesterol content regulate membrane wetting and remodeling by biomolecular condensates

Author

Listed:
  • Agustín Mangiarotti

    (Science Park Golm
    German Center for Neurodegenerative Diseases (DZNE))

  • Elias Sabri

    (Science Park Golm)

  • Kita Valerie Schmidt

    (Science Park Golm
    Thielallee 63)

  • Christian Hoffmann

    (German Center for Neurodegenerative Diseases (DZNE))

  • Dragomir Milovanovic

    (German Center for Neurodegenerative Diseases (DZNE)
    Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health)

  • Reinhard Lipowsky

    (Science Park Golm)

  • Rumiana Dimova

    (Science Park Golm)

Abstract

Biomolecular condensates play a central role in cellular processes by interacting with membranes driving wetting transitions and inducing mutual remodeling. While condensates are known to locally alter membrane properties such as lipid packing and hydration, it remains unclear how membrane composition and phase state in turn affect condensate affinity. Here, we show that it is not only the membrane phase itself, but rather the degree of lipid packing that determines the condensate affinity for membranes. Increasing lipid chain length, saturation, or cholesterol content, enhances lipid packing, thereby decreasing condensate interaction. This regulatory mechanism is consistent across various condensate-membrane systems, highlighting the critical role of the membrane interface. In addition, protein adsorption promotes extensive membrane remodeling, including the formation of tubes and double-membrane sheets. Our findings reveal a mechanism by which membrane composition fine-tunes condensate wetting, highlighting its potential impact on cellular functions and organelle interactions.

Suggested Citation

  • Agustín Mangiarotti & Elias Sabri & Kita Valerie Schmidt & Christian Hoffmann & Dragomir Milovanovic & Reinhard Lipowsky & Rumiana Dimova, 2025. "Lipid packing and cholesterol content regulate membrane wetting and remodeling by biomolecular condensates," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57985-2
    DOI: 10.1038/s41467-025-57985-2
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    References listed on IDEAS

    as
    1. Agustín Mangiarotti & Nannan Chen & Ziliang Zhao & Reinhard Lipowsky & Rumiana Dimova, 2023. "Wetting and complex remodeling of membranes by biomolecular condensates," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Christian Hoffmann & Jakob Rentsch & Taka A. Tsunoyama & Akshita Chhabra & Gerard Aguilar Perez & Rajdeep Chowdhury & Franziska Trnka & Aleksandr A. Korobeinikov & Ali H. Shaib & Marcelo Ganzella & Gr, 2023. "Synapsin condensation controls synaptic vesicle sequestering and dynamics," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Yohan Lee & Sujin Park & Feng Yuan & Carl C. Hayden & Liping Wang & Eileen M. Lafer & Siyoung Q. Choi & Jeanne C. Stachowiak, 2023. "Transmembrane coupling of liquid-like protein condensates," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Claudio Bussi & Agustín Mangiarotti & Christian Vanhille-Campos & Beren Aylan & Enrica Pellegrino & Natalia Athanasiadi & Antony Fearns & Angela Rodgers & Titus M. Franzmann & Anđela Šarić & Rumiana D, 2023. "Stress granules plug and stabilize damaged endolysosomal membranes," Nature, Nature, vol. 623(7989), pages 1062-1069, November.
    5. Claudio Bussi & Agustín Mangiarotti & Christian Vanhille-Campos & Beren Aylan & Enrica Pellegrino & Natalia Athanasiadi & Antony Fearns & Angela Rodgers & Titus M. Franzmann & Anđela Šarić & Rumiana D, 2023. "Publisher Correction: Stress granules plug and stabilize damaged endolysosomal membranes," Nature, Nature, vol. 624(7990), pages 3-3, December.
    6. 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.
    7. Samsuzzoha Mondal & Karthik Narayan & Samuel Botterbusch & Imania Powers & Jason Zheng & Honey Priya James & Rui Jin & Tobias Baumgart, 2022. "Multivalent interactions between molecular components involved in fast endophilin mediated endocytosis drive protein phase separation," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    8. Agustín Mangiarotti & Macarena Siri & Nicky W. Tam & Ziliang Zhao & Leonel Malacrida & Rumiana Dimova, 2023. "Biomolecular condensates modulate membrane lipid packing and hydration," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    9. Merlijn H. I. Haren & Brent S. Visser & Evan Spruijt, 2024. "Probing the surface charge of condensates using microelectrophoresis," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
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