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<p>Biomolecular condensates are membraneless compartments involved in a wide range of cellular processes. Despite their fundamental role in the spatiotemporal regulation of cellular functions, tools for precisely manipulating phase-separated condensates remain limited, and effective methods for discovering and functionalizing tunable phase separation modules from natural proteins are lacking. Here we present a rational engineering approach for androgen receptor (AR) and its clinically used drugs to create a chemical genetic platform, ARDrop, enabling condensates formation and dissolution. This platform is applied to a diverse set of proteins to achieve intended cellular functions, ensuring robust and long-lasting functionality through stable liquid-like properties. Our work develops a powerful toolkit for reversible manipulation of condensates that can be used for dissection of complicated cell signaling, laying the foundation for engineering designer condensates for synthetic biology applications.</p>

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Engineering bi-directional chemically-modulated synthetic condensates for cellular control

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月17日

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  • Ni Zhen,
  • Yue Yan,
  • Guangya Zhu,
  • Tianxin Zhu,
  • Qi Zhang,
  • Qi Chen,
  • Yan Guo,
  • Jidong Zhu,
  • Qiuhui Pan,
  • Jingjing Xie

摘要

Biomolecular condensates are membraneless compartments involved in a wide range of cellular processes. Despite their fundamental role in the spatiotemporal regulation of cellular functions, tools for precisely manipulating phase-separated condensates remain limited, and effective methods for discovering and functionalizing tunable phase separation modules from natural proteins are lacking. Here we present a rational engineering approach for androgen receptor (AR) and its clinically used drugs to create a chemical genetic platform, ARDrop, enabling condensates formation and dissolution. This platform is applied to a diverse set of proteins to achieve intended cellular functions, ensuring robust and long-lasting functionality through stable liquid-like properties. Our work develops a powerful toolkit for reversible manipulation of condensates that can be used for dissection of complicated cell signaling, laying the foundation for engineering designer condensates for synthetic biology applications.