µMap-FFPE: A High-Resolution Protein Proximity Labeling Platform for Formalin-Fixed Paraffin-Embedded Tissue Samples

Many disease states can be understood by elucidating small-scale biomolecular protein interaction networks, or microenvironments. Recently, photoproximity labeling methods, like µMap, have emerged as high-resolution techniques to study key spatial relationships in subcellular architectures. However, in vitro models typically lack cell type heterogeneity and three dimensionality, integral parameters that limit the translation of in vitro findings to the clinic. To this end, formalin-fixed paraffin-embedded (FFPE) tissues serve as an invaluable model system for biomedical research by fixing complex multi-cell interaction networks in their natural environment. Thus, identifying microscale interactions in these samples would provide important clinical insight. Yet, the underlying chemistry of photoproximity labeling is challenged by formalin-fixation and de-crosslinking, precluding its application. Herein, we report the development of competent labeling system, µMap-FFPE, enabling the comparison of CD20’s interactome between healthy and cancerous cells or preserved patient tissues.