Detection of Lipids and Proteins on Biological Surfaces using Imaging Mass Spectrometry

Doctoral thesis, 2016

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a technique that can be used for imaging the spatial distribution of many different molecules at the same time. It is very sensitive for detection of small biomolecules, such as lipids, whereas larger biomolecules, such as peptides and proteins, cannot be detected as intact entities due to fragmentation. In this work, we have explored an alternative approach for detection of peptides and proteins with ToF-SIMS, using liposomes for labeling the target of interest. In this way, both lipids and proteins can be imaged at the same time, which opens up for the opportunity to investigate lipid-protein interactions. The method has been applied for detection of biomolecules on two different biological surfaces; (1) a model surface containing controlled concentrations of target biomolecules bound to the substrate and (2) brain tissue sections from Alzheimer’s disease transgenic mice. Other techniques, such as fluorescence microscopy and quartz crystal microbalance with dissipation monitoring (QCM-D), have also been used for the characterization of liposomes binding to the surface. Another imaging mass spectrometry technique, matrix-assisted laser desorption/ionization (MALDI), was also employed on mouse brain tissue sections for detection and investigation of amyloid-β deposits, a peptide associated with Alzheimer’s disease. This thesis thus shows how different techniques can be combined for investigation of biomolecules on complex biological surfaces, in order to potentially provide new information about the mechanism of neurodegeneration in Alzheimer’s disease.