MALDI mass spectrometry imaging of extracellular matrix proteins

The identity, quantity, and spatial distribution of extracellular matrix (ECM) proteins in tissues defines the function of cells within. Dysregulation of ECM proteins can be coincident with or even drive various pathological conditions. Common techniques that are used to spatially detect and identify ECM proteins include magnetic resonance imaging (MRI), immunohistochemistry (IHC), second harmonic generation (SHG) imaging, and scanning electron microscopy (SEM). However, these techniques typically limit detection to only a few proteins simultaneously. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has emerged as a tool capable of detecting various biomolecules such as lipids, proteins, peptides, and glycans in a spatially-defined manner due to its high molecular specificity. However, it is rarely applied to ECM proteins because of their highly cross-linked nature, relatively low abundance, and prevalence of post-translational modifications. This perspective discusses the current state and future of MALDI-MSI of ECM proteins, details the technical hurdles limiting the adoption of MALDI-MSI for ECM imaging, and summarizes the potential opportunities that MALDI-MSI has for spatially resolving ECM proteins in healthy and diseased tissues.