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

Area of Science:

• Biochemistry and Molecular Biology
• Analytical Chemistry
• Mass Spectrometry Imaging

Background:

• Lipids are crucial biomolecules involved in cellular signaling and energy storage, exhibiting significant structural diversity.
• Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) enables spatial mapping of lipids in biological tissues.
• Distinguishing between isobaric and isomeric lipids is a major challenge in MALDI-IMS due to limited mass-to-charge (m/z) resolution.

Purpose of the Study:

• To investigate the utility of trapped ion mobility spectrometry (TIMS) coupled with MALDI-IMS for enhanced lipid isomer separation and imaging.
• To demonstrate the capability of MALDI-TIMS-MS in deconvoluting complex lipid mixtures and resolving various lipid isomers.

Main Methods:

• Utilized a MALDI quadrupole time-of-flight (Q-TOF) mass spectrometer integrated with trapped ion mobility spectrometry (TIMS).
• Separated and analyzed lipid isomer standards, including backbone, acyl chain, double-bond position, and stereoisomers.
• Performed in situ separation and imaging of lipid isomers in whole-body mouse pup tissue sections.

Main Results:

• Achieved a >250% increase in peak capacity for ion mobility spectrometry (IMS) experiments using MALDI-TIMS-MS.
• Successfully demonstrated the separation of diverse lipid isomer classes, highlighting improved resolution.
• Visualized distinct spatial distributions of lipid isomers within tissue sections, validating the imaging capabilities.

Conclusions:

• MALDI-TIMS-MS significantly enhances the separation power for lipid isomer analysis in IMS.
• This integrated approach effectively deconvolutes complex lipid mixtures and improves the characterization of lipid structural diversity.
• The technique holds promise for advanced lipidomics studies and molecular imaging applications in biological research.