A multimodal mass spectrometry imaging approach for the study of musculoskeletal tissues

Abstract

Imaging mass spectrometry combines the chemical sensitivity and specificity of mass spectrometry with microscopic imaging resolution. The ability to simultaneously obtain images from detected analytes allows us to know the composition of the surface of a thin tissue section. Although the technology is very well known and different applications have been used like in the classification of different diseases, little has been done in musculoskeletal tissues. Rheumatoid Arthritis (RA) is a widespread musculoskeletal disease that exhibits an extensive molecular complexity that is poorly understood. In this paper a multimodal mass spectrometry imaging (MSI) strategy was applied to identify and localize biomolecules such as lipids, peptides and proteins in bone, muscle or skin from the limb of a mouse model of RA. High spatial resolution Secondary Ion Mass Spectrometry (SIMS) imaging was used to image the elemental and small molecular distributions. Matrix Assisted Laser Desorption/Ionization (MALDI) imaging complemented these studies revealing a specific distribution of phospholipids and peptides/proteins. A protocol that employs “on tissue digestion/off tissue analysis” was established for orthogonal peptide/protein identification. Among the identified proteins were cytokines (like interleukin-18), cytoskeleton related proteins (actin, tubulin or myosin) or proteins of the family of metalloproteinases that are involved in inflammation triggering and autoimmune responses in RA. The results of this multimodal MSI and complementary proteomics approach resulted in a multitude of protein localizations and local interactions that reveal detailed molecular signatures from the different regions that constitute the musculoskeletal tissues affected by RA. The information provided by multimodal SIMS imaging and MALDI-MSI, reveals new and future possibilities for the study of musculoskeletal diseases.