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journal article·2026-07-16Open access

A Bright Ratiometric Dipyrene Probe for Functional Imaging of Condensate Microenvironments in Living Cells

Koki Matsumoto, Sora Kitai, Yoshio Nishiyama, Shogo Amemori, Kei Makiyama, Dini Kurnia Ikliptikawati, Kentaro Ohira, Yuta Kozuka, Maho Tobita, Shih‐Cheng Chen, Chien‐Hung Yu, Wei‐Min Liu, De‐Chen Lin, Motohiro Mizuno, Kazuma Ogawa, Koichi Ogami, Kenji Takahashi, Hiroshi I. Suzuki, Richard W. Wong, Takahiro Soeta, Masaharu Hazawa

Advanced Science
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Abstract

ABSTRACT Biomolecular condensates exhibit spatially heterogeneous microenvironments shaped by intertwined physicochemical factors, yet practical small‐molecule tools for mapping these states in living cells remain limited. Here, we report PyLUMI, a bright dipyrene ratiometric probe, optimized by linker engineering to improve fluorescence output under aqueous conditions while preserving excimer‐to‐monomer (E/M) readout capability. Solution‐phase characterization identifies a scaffold with enhanced fluorescence efficiency and an E/M response to coupled polarity–viscosity microenvironmental changes. In recombinant protein condensates, PyLUMI provides substantially increased signal and enables pixel‐resolved visualization of intra‐condensate heterogeneity. In living cells, the probe enables low‐exposure ratiometric imaging of centrosome‐associated condensate compartments and reveals microenvironmental signatures linked to cell‐cycle progression and pathology‐associated centrosome amplification beyond morphological size differences. These results establish PyLUMI as a functional chemical reporter for spatially resolved profiling of integrated physicochemical fingerprints in condensate‐associated compartments.
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Research context

OpenAlex topics: Advanced Fluorescence Microscopy Techniques · Luminescence and Fluorescent Materials · Molecular Sensors and Ion Detection

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Affiliations

Division of Transdisciplinary Sciences Graduate School of Frontier Science Initiative Kanazawa University Kanazawa Ishikawa Japan

Division of Material Sciences Graduate School of Natural Science and Technology Kanazawa University Kanazawa Japan

Institute for Frontier Science Initiative Kanazawa University Kanazawa Ishikawa Japan

NanoMaterials Research Institute Kanazawa University Kanazawa Japan

School of Chemistry College of Science and Engineering Kanazawa University Kanazawa Japan

Division of Biological Science and Technology Graduate School of Natural Science and Technology Kanazawa Ishikawa Japan

National Institute of Cancer Research National Health Research Institutes Tainan City Taiwan

Department of Biochemistry and Molecular Biology College of Medicine National Cheng Kung University Tainan City Taiwan

Institute of Basic Medical Sciences, College of Medicine National Cheng Kung University Tainan City Taiwan

Department of Chemistry Fu Jen Catholic University New Taipei City Taiwan

Center for Craniofacial Molecular Biology Herman Ostrow School of Dentistry University of Southern California Los Angeles California USA

Norris Comprehensive Cancer Center University of Southern California Los Angeles California USA

Graduate School of Medical Sciences Kanazawa University Kanazawa Ishikawa Japan

Division of Molecular Oncology Center for Neurological Diseases and Cancer Nagoya University Graduate School of Medicine Nagoya Aichi Japan

Institute for Glyco‐Core Research (iGCORE) Nagoya University Nagoya Aichi Japan

Center for One Medicine Innovative Translational Research (COMIT) Nagoya University Nagoya Aichi Japan

Inamori Research Institute for Science (InaRIS) Kyoto Japan

WPI Nano Life Science Institute Kanazawa University Kanazawa Ishikawa Japan

Funding

Japan Agency for Medical Research and Development

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