Resolving the Complexity of Spatial Lipidomics Using MALDI TIMS Imaging Mass Spectrometry

Abstract

<p>Lipids are a structurally diverse class of molecules with important biological functions including cellular signaling and energy storage. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) allows for direct map-ping of biomolecules in tissue. Fully characterizing the structural diversity of lipids remains a challenge due to the presence of isobaric and isomeric species, which greatly complicates data interpretation when only <i>m/z </i>information is available. Integrating ion mobility separations aids in deconvoluting these complex mixtures and addressing the challenges of lipid IMS. Here we demonstrate that a MALDI quadrupole time-of-flight (Q-TOF) mass spectrometer with trapped ion mobility spectrometry (TIMS) enables approximately a ~270% increase in the peak capacity during IMS experiments. MALDI TIMS-MS separation of lipid isomer standards, including sn-backbone isomers, acyl chain isomers, as well as double bond positional and geometric isomers are demonstrated. As a proof-of-concept, <i>in situ </i>separation and imaging of lipid isomers with distinct spatial distributions was performed using tissue sections from a whole-body mouse pup.</p>

Multimodal Imaging Based on Vibrational Spectroscopies and Mass Spectrometry Imaging Applied to Biological Tissue: A Multiscale and Multiomics Review

“…In a recent MSI example involving trapped IM-MS (TIMS), Djambazova et al showed a 271% increase in molecular species detected between m/z 680-880 by applying a 650 ms separation. 187 Of course, this adds another dimension to the already highly dimensional MSI data and tools need to be developed to visualize it. Yet, having two points of data, CCS and m/z, databases would provide more structural information than MS without IM-MS. 185 Another interesting challenge as IM-MS becomes more integral to MALDI-MSI is inconsistencies among researchers in how they report their IM-MS data, and even debate over what is actually measured.…”