Nanomaterial signatures program biomolecular condensates via triphasic separation for chemoplasticity remodeling

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 () and Da Huo ()
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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

Nature Communications, 2025, vol. 16, issue 1, 1-24

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-64623-4

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