Tools for Intersectional Optical and Chemical Tagging on Cell Surfaces

Area of Science:

• Cell biology
• Chemical biology
• Biotechnology

Background:

• Precise and controllable labeling of live cells is crucial for understanding cellular processes.
• Existing chemical labeling methods often lack spatial or temporal control.
• Developing versatile tools for multimodal cell analysis is an ongoing challenge.

Purpose of the Study:

• To introduce photocaged tetrazines as adaptable "photo-click" adapters for cell tagging.
• To integrate light-gating into established chemical labeling techniques.
• To demonstrate novel applications in live cell analysis and sorting.

Main Methods:

• Synthesis of novel functionalized photocaged tetrazine structures.
• Application of photocaged tetrazines to HaloTag/chloroalkane, amine, and antibody labeling.
• Demonstration in live cultured cells, zebrafish embryos, and cell sorting.

Main Results:

• Successful implementation of light-gated versions of three common cell-targeting chemical methods.
• Demonstration of photoclick adapters for monitoring tissue flow in zebrafish embryos.
• Enabled combinatorial multicolor labeling and sorting of optically defined cell populations.

Conclusions:

• Photocaged tetrazines provide optical control over cell tagging schemes.
• The modularity of photo-click adapters allows for flexibility in tag and cell attachment chemistry.
• These tools offer versatile solutions for advanced live cell imaging and manipulation.