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Galectin Trafficking Pathway-Enabled Color-Switchable Detection of Lysosomal Membrane Permeabilization
1Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory for Physical Chemistry of Solid Surfaces, the Key Laboratory for Chemical Biology of Fujian Province, and The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Xiamen University, Xiamen 361005, China.
Insights
Researchers developed a novel imaging method for lysosomal membrane permeabilization (LMP) using targeted glyco-dendrimers. This technique detects LMP, a key factor in human diseases, by observing a red-to-green fluorescence switch in affected lysosomes.
Area of Science:
- Biomedical imaging
- Cell biology
- Molecular diagnostics
Background:
- Lysosomal membrane permeabilization (LMP) is implicated in various human diseases.
- Cytosolic galectins relocate to lysosomes during LMP.
- Existing methods for detecting LMP have limitations.
Purpose of the Study:
- To develop a novel galectin trafficking-targeted method for imaging LMP.
- To utilize synthetic glyco-dendrimers for sensitive and specific LMP detection.
- To differentiate LMP-positive lysosomes from physiological and pH-elevated lysosomes.
Main Methods:
- Design and synthesis of two glyco-dendrimers: a sialic acid-terminated probe (red fluorescent) and a lactose-terminated probe (green fluorescent).
- Exploitation of galectin binding and lysosomal pH changes for differential fluorescence signaling.
- Imaging of LMP in distinct cell death pathways using the developed probes.
Main Results:
- Both dendrimers accumulated in physiological lysosomes.
- The red fluorescent probe was released from LMP+ lysosomes, while the green fluorescent probe was retained due to galectin binding.
- LMP+ lysosomes showed a characteristic red-to-green fluorescence switch, indicating loss of acidity and galectin accumulation.
Conclusions:
- The developed galectin trafficking-targeted glyco-dendrimers enable effective imaging of LMP.
- This red-to-green color switch provides a reliable method for discerning LMP+ lysosomes.
- The probes offer utility for detecting LMP in various disease contexts and cell death pathways.
Abstract:
Lysosomal membrane permeabilization (LMP) engaged in multiple human diseases is accompanied by relocation of cytosolic galectin into LMP+ lysosomes. We herein reported a galectin trafficking-targeted method to image LMP using two kinds of glyco-dendrimers, a sialic acid-terminated dendrimer labeled with pH-inert rhodamine and a lactose-terminated dendrimer labeled with fluorescein that becomes green-emissive in pH-elevated lysosomes. Albeit both accumulated in physiological lysosomes, the former is released from LMP+ lysosomes while the latter binds to galectin accumulated in LMP+ lysosomes and thus trapped in LMP+ lysosomes. Accordingly, LMP+ lysosomes exhibit loss of red fluorescence and turn-on green fluorescence due to loss of lysosomal acidity. This red-to-green color switch enables discernment of LMP+ lysosomes from physiological lysosomes and pH-elevated lysosomes and can be further utilized to detect LMP in distinct cell death pathways. These results suggest the utility of galectin trafficking pathway-integrated synthetic probes for detection of LMP, a key factor for diseased cells.
