A strategy for mapping the distribution of thousands of proteins across whole-tissue slice samples with high accuracy is reported in Nature Communications this week. The approach, its developers write, will aid efforts to understand the spatially organized biological regulations responsible for disease mechanisms and drug actions. The ability to precisely map proteins in-depth at whole-tissue levels provides comprehensive insights into the spatially organized regulatory processes/networks in tissues but is technically challenging. But a group of researchers from the University at Buffalo has now developed a pipeline — dubbed micro-scaffold-assisted spatial proteomics, or MASP — capable of acquiring the distribution maps for thousands of proteins across a whole-tissue slice at high quantitative quality. The process involves tissue micro-compartmentalization using a 3D-printed micro-scaffold; extraction, clean-up, and digestion of the location-specific micro-specimens followed by liquid chromatography-mass spectrometry analysis; and the generation of protein distribution following accurate protein quantification. The scientists demonstrate MASP by mapping more than 5,000 cerebral proteins in the mouse brain encompassing numerous important brain markers, regulators, and transporters, many of which had not previously been mapped on the whole-tissue level.