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<p>Liquid–liquid phase separation is an important biomolecular process in the formation of membraneless intracellular organelles that has inspired the development of artificial droplet systems. We developed caged coacervating peptides (CCPs) based on a histidine-rich squid beak protein sequence. The peptides were caged with a photodeprotectable (7-diethylaminocoumarin-4-yl)methoxycarbonyl group. The CCPs formed coacervates in the caged state and were partially dispersed upon blue-light irradiation. Photo-uncaging occurred rapidly, inducing coacervate dispersion. A mutant CCP with reduced π–π interactions exhibited efficient photo-dependent disassembly and enabled the encapsulation and release of a fluorescently labeled adenosine 5′-triphosphate (Bodipy-ATP) upon irradiation. These CCPs offer an efficient light-controlled approach for biomolecular encapsulation within coacervates and targeted drug delivery.</p>

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Liquid–liquid phase separation by caged coacervating peptides

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月25日

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  • Akinari Bando,
  • Mizuki Kitamatsu,
  • Yuuki Kanazaki,
  • Rika Tojo,
  • Kazunori Watanabe,
  • Takashi Ohtsuki

摘要

Liquid–liquid phase separation is an important biomolecular process in the formation of membraneless intracellular organelles that has inspired the development of artificial droplet systems. We developed caged coacervating peptides (CCPs) based on a histidine-rich squid beak protein sequence. The peptides were caged with a photodeprotectable (7-diethylaminocoumarin-4-yl)methoxycarbonyl group. The CCPs formed coacervates in the caged state and were partially dispersed upon blue-light irradiation. Photo-uncaging occurred rapidly, inducing coacervate dispersion. A mutant CCP with reduced π–π interactions exhibited efficient photo-dependent disassembly and enabled the encapsulation and release of a fluorescently labeled adenosine 5′-triphosphate (Bodipy-ATP) upon irradiation. These CCPs offer an efficient light-controlled approach for biomolecular encapsulation within coacervates and targeted drug delivery.