The Use of High-Resolution Ion Mobility for Structural Insight into Consequential Lipid Membrane Biology

The inclusion of ion mobility into lipidomic workflows is rapidly becoming more common. The gas-phase separation afforded by ion mobility is complementary and cumulative to chromatographic separations and shotgun approaches. The benefits of using ion mobility are the generation of physio-chemical parameters (e.g., collisional-cross section (CCS) values) and reduction of mass spectral ambiguity resulting from isobaric and isomeric overlap. Combined, these benefits enable more robust and confident identification of lipid structures especially when confronted with complex sample matrices. Similar to other analytical techniques (e.g., chromatography and mass spectrometry), the utility and impact of ion mobility is greatly enhanced by increasing the resolution magnitude of the acquired data.

In the case of drift tube ion mobility on the Agilent 6560 platform, the use of high resolution demultiplexing (HRdm) pushes the effective resolving power of the ion mobility separation to a level where gas-phase separation of lipid isomers is achieved. We will demonstrate the advantages of including high-resolution ion mobility for lipid isomer identification in both LC-MS/MS and shotgun workflows. Specifically, we will highlight recent work from our lab to characterize intact oxidized membrane lipids using a multidimensional analytical workflow incorporating orthogonal chromatographic separations, ion mobility with HRdm, and tandem MS. Additionally, we will showcase our recent work to combine ion mobility with adduct consolidation to reduce isobaric interference, increase sensitivity, and maximize gas-phase separation to identify diastereomeric glycosphingolipids in viral envelope membranes.

Presenter: Jace W. Jones, Ph.D. (Assistant Professor, Associate Director of the Mass Spectrometry Center, Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy)

Dr. Jace W. Jones is an Assistant Professor and Associate Director of the Mass Spectrometry Center at the University of Maryland, School of Pharmacy. Dr. Jones received his BS degree from Whitworth University and PhD from the Department of Chemistry at the University of Washington. Prior to his current positon, he spent several years in industry and academia. His research program seeks to understand the synergistic relationship between chemistry and biology, and how this profound interaction influences human health. Specifically, his lab is focused on developing analytical platforms, based on chromatography, ion mobility, and mass spectrometry, to probe the structure/function dynamics of lipids. The knowledge gained by comprehensively characterizing lipid structure and precisely anchoring structure to biological function provides a unique opportunity to expound fundamental knowledge of disease/injury and provide insight for drug development targets.