Mapping dynamic changes in lysosomal polarity with a sensitive and large stokes shift fluorescent probe

Area of Science:

• Cell Biology
• Chemical Biology
• Biomedical Imaging

Background:

• Lysosomal polarity is crucial for cellular function and disease progression.
• Existing fluorescent probes for lysosomal polarity have limitations like small Stokes shifts and low sensitivity, hindering accurate dynamic tracking.

Purpose of the Study:

• To develop a novel, highly sensitive lysosome-targeted fluorescent probe for monitoring lysosomal polarity.
• To overcome the limitations of current probes, enabling high-fidelity imaging and real-time tracking of lysosomal dynamics.

Main Methods:

• Design and synthesis of a novel fluorescent probe (PTC) based on intramolecular charge transfer (ICT) effect.
• Characterization of PTC's photophysical properties, including sensitivity to microenvironmental polarity and Stokes shift.
• Application of PTC for high-fidelity imaging of lysosomal polarity and real-time monitoring of cellular processes like autophagy.

Main Results:

• The developed probe PTC exhibits high sensitivity to microenvironmental polarity with a good linear response.
• PTC demonstrates a remarkably large Stokes shift (>165 nm), minimizing auto-fluorescence interference.
• Successful high-fidelity imaging of lysosomal polarity, detection of autophagy, and real-time capture of lysosomal dynamics were achieved.

Conclusions:

• The novel fluorescent probe PTC provides a powerful chemical tool for studying lysosomal function.
• PTC enables accurate assessment of cellular status and lysosome-related disease mechanisms.
• This probe facilitates in-depth research into the molecular mechanisms underlying lysosome-related diseases.