mu Map-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 ourability to interrogate cell- and tissue-level microenvironments in animal models. Here, we report mu Map-Red, a proximity labelingplatform that uses a red-light-excited SnIVchlorin e6 catalyst to activate a phenyl azide biotin probe. We validate mu Map-Red bydemonstrating photonically controlled protein labelingin vitrothrough several layers of tissue, and we then apply our platformincelluloto labelEGFRmicroenvironments and validate performance with STED microscopy and quantitative proteomics. Finally, todemonstrate labeling in a complex biological sample, we deploy mu Map-Red in whole mouse blood to profile erythrocyte cell-surfaceproteins. This work represents a significant methodological advance toward light-based proximity labeling in complex tissueenvironments and animal models.