μMap-Red: Proximity Labeling by Red Light Photocatalysis

Modern proximity labeling techniques
have enabled significant advances
in understanding biomolecular interactions. However, current tools
primarily utilize activation modes that are incompatible with complex
biological environments, limiting our ability to interrogate cell-
and tissue-level microenvironments in animal models. Here, we report
μMap-Red, a proximity labeling platform that uses a red-light-excited
SnIV chlorin e6 catalyst to activate a phenyl azide biotin
probe. We validate μMap-Red by demonstrating photonically controlled
protein labeling in vitro through several layers
of tissue, and we then apply our platform in cellulo to label EGFR microenvironments and validate performance
with STED microscopy and quantitative proteomics. Finally, to demonstrate
labeling in a complex biological sample, we deploy μMap-Red
in whole mouse blood to profile erythrocyte cell-surface proteins.
This work represents a significant methodological advance toward light-based
proximity labeling in complex tissue environments and animal models.