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Nanomaterial signatures program biomolecular condensates via triphasic separation for chemoplasticity remodeling

Author

Listed:
  • Liu-Ting Zheng

    (Nanjing Medical University)

  • Zeng-Shuai Yan

    (Soochow University)

  • Xin-Yue Li

    (Nanjing Medical University)

  • Jia-Jia Chang

    (Nanjing Medical University)

  • Xiao-Qi Tan

    (Nanjing Medical University)

  • Yu-Xing Wang

    (Nanjing Medical University)

  • Hong-Ming Ding

    (Soochow University)

  • Qin Liu

    (Nanjing University)

  • Yu-Qiang Ma

    (Nanjing University)

  • Da Huo

    (Nanjing Medical University)

Abstract

Membraneless organelles form by phase separation and regulate cell behavior. We show that cholesterol-patterned AuNPs program nanomaterial-induced stress granules (NSGs) by lowering G3BP1 condensation barriers through a solid–liquid–liquid triphasic sequence: nanomaterials recruit hnRNPC, which then engages G3BP1 to nucleate gel-like condensates. We map NSG microenvironments (temperature, polarity, pH, and proteasome activity), uncover dual disassembly—a slow VCP/19S-dependent route and a rapid SUMO/20S-dependent backup—and show that NSGs remodel chemo-plasticity: they mitigate doxorubicin/cisplatin toxicity in normal tissues yet sensitize tumors to nocodazole in vivo. Local induction and selective dissolution of NSGs thus offers a strategy to decouple efficacy from toxicity. Our results establish design rules linking nanomaterial surface chemistry to condensate programming and provide actionable levers to steer therapeutic outcomes.

Suggested Citation

  • Liu-Ting Zheng & Zeng-Shuai Yan & Xin-Yue Li & Jia-Jia Chang & Xiao-Qi Tan & Yu-Xing Wang & Hong-Ming Ding & Qin Liu & Yu-Qiang Ma & Da Huo, 2025. "Nanomaterial signatures program biomolecular condensates via triphasic separation for chemoplasticity remodeling," Nature Communications, Nature, vol. 16(1), pages 1-24, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64623-4
    DOI: 10.1038/s41467-025-64623-4
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    References listed on IDEAS

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