Spatial Proteomics Analysis of Extracellular Matrix-Rich Tissues

Mass spectrometery (MS)-based proteomics analysis is a powerful tool that allows for an in-depth understanding of the protein composition, including protein post-translational modifications, of a sample. Classic bulk MS methods on tissues usually results in a loss of resolution, particularly on the protein composition that defines morphological features. Further, many patient-derived samples are preserved using the formalin-fixed paraffin-embedded (FFPE) method due to ease of storage. These methods present a barrier to MS, leading to low yield. Here, we describe a method using laser-capture microdissection on FFPE tissue sections to isolate specific regions of interest, coupled with modified MS proteomics sample preparation to maximize protein yield, allowing us to spatially identify and quantify protein changes in tissues.