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Mapping Endocytic Vesicular Acidification with a pH-Responsive DNA Nanomachine
Xiaodong Xie1, Zhiyuan Liu1, Xuelin Xiang2
1School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 20024, China.
Chembiochem : a European Journal of Chemical Biology
|August 21, 2024
Summary
Researchers developed a pH-responsive DNA nanomachine to track cellular pH changes during endocytosis. This tool reveals differences in vesicle acidification between normal and cancer cells, aiding disease pathology studies.
Area of Science:
- Biotechnology
- Molecular Biology
- Cell Biology
Background:
- Understanding cellular pH dynamics is crucial for cell health and disease.
- Endocytic vesicular acidification is a key process in cellular function.
Purpose of the Study:
- To develop a novel pH-responsive DNA nanomachine for sensing endocytic vesicle acidification.
- To enable spatiotemporal tracking of pH changes during endosomal maturation.
Main Methods:
- Integration of a pH-sensitive i-motif and fluorescence resonance energy transfer (FRET) into a tetrahedral DNA framework (TDF).
- Utilizing pH-triggered spatial proximity modulation of FRET for pH sensing (pH 7.0 to 5.5).
- Leveraging TDF's endo-lysosome-targeting ability for cellular tracking.
Main Results:
- Demonstrated efficient pH sensing within the endocytic pathway.
- Successfully tracked endocytic vesicle acidification in real-time.
- Observed significant differences in acidification between normal and cancer cells at the single-spot level.
Conclusions:
- The developed DNA nanomachine provides a universal platform for studying vesicle acidification-related pathologies.
- Highlights potential applications in distinguishing cellular states, such as normal vs. cancer cells, based on pH dynamics.

