A translocation fluorescent probe for analyzing cellular physiological parameters in neurological disease models

Area of Science:

• Molecular probes for neuroscience
• Cellular physiology imaging

Background:

• Neurological disorders correlate with altered cell membrane permeability (CMP) and mitochondrial membrane potential (MMP).
• Simultaneous monitoring of CMP and MMP is crucial for assessing nerve cell health and diagnosing neurological diseases but remains challenging.

Purpose of the Study:

• To design and synthesize novel fluorescent probes for simultaneous CMP and MMP monitoring.
• To investigate the organelle-staining behavior and intracellular translocation of these probes.
• To validate the probes' utility in imaging CMP and MMP changes in neurological disease models.

Main Methods:

• Synthesis of two quinolinium-carbazole-derivated fluorescent probes (OQ and PQ) with subtle structural differences.
• Organelle-specific staining and intracellular translocation studies.
• Combined experimental, molecular dynamics simulations, and density functional theory calculations to elucidate probe mechanisms.
• Application of probe OQ in cell models of oxidative stress, Parkinson's disease, and viral infection.

Main Results:

• Probes OQ and PQ exhibited distinct organelle-targeting behaviors.
• OQ demonstrated simultaneous staining of cell membranes and mitochondria, with CMP/MMP-dependent translocation to the nucleus.
• OQ successfully monitored continuous CMP and MMP changes in neurological disease-related cell models.

Conclusions:

• The subtle structural difference between OQ and PQ dictates their unique intracellular translocation properties.
• OQ serves as a valuable intracellular translocation probe for real-time imaging of CMP and MMP dynamics.
• This work provides a novel imaging tool for neurological disease research and a strategy for designing disease-specific probes.