μMap-Red: Proximity Labeling by Red Light Photocatalysis. Author Benito Buksh, Steve Knutson, James Oakley, Noah Bissonnette, Daniel Oblinsky, Michael Schwoerer, Ciaran Seath, Jacob Geri, Frances Rodriguez-Rivera, Dann Parker, Gregory Scholes, Alexander Ploss, David MacMillan Publication Year 2022 Type Journal Article Abstract 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 Sn chlorin e6 catalyst to activate a phenyl azide biotin probe. We validate μMap-Red by demonstrating photonically controlled protein labeling through several layers of tissue, and we then apply our platform to label 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. Keywords Animals, Mice, Membrane Proteins, Light, Proteomics, Staining and Labeling, Biotin Journal J Am Chem Soc Volume 144 Issue 14 Pages 6154-6162 Date Published 2022 Apr 13 ISSN Number 1520-5126 DOI 10.1021/jacs.2c01384 Alternate Journal J Am Chem Soc PMCID PMC9843638 PMID 35363468 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML