Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging for Peptide and Protein Analyses: A Critical Review of On-Tissue Digestion

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has established itself among the plethora of mass spectrometry applications. In the biomedical field, MALDI-MSI is being more frequently recognized as a new method for the discovery of biomarkers and targets of treatment, classification of diseased and healthy tissues, or prediction of the outcome of a pathology. The technology has been used to study the localization of proteolytic peptides directly on tissue sections. A direct correlation between the detected peptides and the distribution and identity of the original precursor protein is the ultimate goal of any MALDIMSI experiment. Enzymatic digestion protocols are commonly used to reveal the protein signature of these complex tissues. Considerations that pertain to methods of sample preparation, on-tissue digestion, data analysis, and visualization will be addressed. This review will also discuss selected applications of on-tissue digestion combined with the MALDI-MSI technology in biomedicine