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. Photoproximity
labeling methods, like μMap, have recently emerged as high-resolution
techniques for mapping spatial relationships within subcellular architectures.
However, in vitro models typically utilized lack
the cell-type heterogeneity and three-dimensional structure essential
for translating findings to clinical settings. To this end, formalin-fixed
paraffin-embedded (FFPE) tissues are invaluable model systems for
biomedical research, as they preserve complex multicellular interaction
networks in their natural environment. While identifying microscale
interactions in these samples could provide critical clinical insights,
chemical modifications introduced during formalin-fixation and de-cross-linking
are incompatible with standard photoproximity labeling techniques.
Herein, we introduce μMap-FFPE, a new labeling system that enables
comparison of the CD20 interactome across healthy cells, cancerous
cells, and preserved patient tissues.