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A Bright Ratiometric Dipyrene Probe for Functional Imaging of Condensate Microenvironments in Living Cells
Koki Matsumoto1, Sora Kitai2, Yoshio Nishiyama2
1Division of Transdisciplinary Sciences, Graduate School of Frontier Science Initiative, Kanazawa University, Kanazawa, Ishikawa, Japan.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 16, 2026
Summary
PyLUMI is a new chemical probe that maps microenvironments within biomolecular condensates. This bright dipyrene probe enables visualization of cellular heterogeneity, aiding in understanding cell cycle and disease states.
Area of Science:
- Chemical Biology
- Biophysics
- Cell Biology
Background:
- Biomolecular condensates have complex microenvironments influenced by various factors.
- Existing tools for mapping these microenvironments in living cells are limited.
- Understanding condensate microenvironments is crucial for cellular function and disease.
Purpose of the Study:
- To develop a novel small-molecule tool for mapping microenvironmental states within biomolecular condensates.
- To create a bright dipyrene ratiometric probe, PyLUMI, with enhanced performance in aqueous conditions.
- To utilize PyLUMI for visualizing intra-condensate heterogeneity and microenvironmental signatures in living cells.
Main Methods:
- Designed and optimized PyLUMI, a dipyrene ratiometric probe, through linker engineering.
- Characterized PyLUMI's fluorescence properties and response to polarity-viscosity changes in solution.
- Applied PyLUMI for imaging in recombinant protein condensates and in living cells, including centrosome-associated compartments.
Main Results:
- PyLUMI exhibits enhanced fluorescence efficiency and maintains excimer-to-monomer (E/M) ratio readout.
- The probe enables pixel-resolved visualization of heterogeneity within recombinant protein condensates.
- PyLUMI allows low-exposure ratiometric imaging in living cells, revealing microenvironmental signatures linked to cell cycle and pathology.
Conclusions:
- PyLUMI is a functional chemical reporter for profiling physicochemical fingerprints in condensate-associated compartments.
- The probe facilitates spatially resolved imaging of microenvironmental states in living cells.
- PyLUMI offers new insights into cellular processes and disease mechanisms involving biomolecular condensates.
