Mapping Extracellular Matrix Proteins in Formalin-Fixed, Paraffin-Embedded Tissues by MALDI Imaging Mass Spectrometry

Collagens and elastin form the fundamental framework of all tissues and organs, and their expression and post-translational processing are tightly regulated in disease and health. Because of their unique structural composition and properties, it is a recognized challenge to access these protein structures within the complex tissue microenvironment to understand how localized changes modulate tissue health. We describe a new workflow using a combination of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) with matrix metalloproteinase (MMP) enzymes to access and report on spatial localization of collagen and elastin sequences in formalin-fixed, paraffin-embedded (FFPE) tissues. The developed technology provides new access to collagens and elastin sequences localized to tissue features that were previously unattainable. This high-throughput technological advance should be applicable to any tissue regardless of disease type, tissue origin, or disease status and is thus relevant to all research: basic, translational, or clinical.