Glycolipids, simply “fatty sweet” molecules, are a relatively unexplored category of lipids. A novel approach developed by an Austrian team led by chemist Evelyn Rampler of the University of Vienna has now revealed greater insights into the functioning of particular glycolipids present on the surfaces of stem cells. The technique outlined by the researchers from the University of Vienna, BOKU Vienna and the University of Graz in the open-access Journal of the American Chemical Society Au may be used for a broad variety of glycolipid classes.
Pioneering achievements in glycoscience for establishing the role of sugar compounds on cell surfaces recently got acknowledgement with the Nobel Prize in Chemistry granted to Carolyn Bertozzi. However, research into the family of fatty sweet molecules called glycolipids is a very young, growing topic of study. With their new findings, chemist Evelyn Rampler of the University of Vienna and her colleagues are delivering crucial foundational research for this field. Using very sensitive methods such as mass spectrometry, the structural characteristics of glycolipids may be examined.
Decoding of gangliosides
This work aims at creating a measuring and data analysis approach for a particular class of relatively unknown glycolipids, so-called gangliosides, whose composition varies on the cell membrane during stem cell development.
“Previous techniques have not been able to identify the many activities of gangliosides in Alzheimer’s disease, dementia or cancer because they lacked the requisite sensitivity. With our novel approach, we now give a tool for the thorough study of gangliosides,” explains Evelyn Rampler, group head at the Institute of Analytical Chemistry at the University of Vienna.
A research partnership between the Medical University Vienna and the University of Vienna will now explore the importance of gangliosides and other fatty sweet compounds in cancer. To monitor sugar structures on cells with even greater precision, it would be also conceivable to integrate this new approach with the bioorthogonal labelling established by Nobel Prize winner Carolyn Bertozzi.
Study of human stem cells
“Our investigation on human stem cells has shown that the current patterns of gangliosides alter substantially depending on which cells or tissues are grown from the stem cells. It was consequently feasible to uncover novel markers for distinct cell types, which now have to be verified in independent investigations incorporating bigger sample numbers,” explains Evelyn Rampler.
“Based on our novel mass spectrometry approach, we were able to detect and characterise the chemical diversity of gangliosides at an unprecedented degree of detail,” explains first author and chemist Katharina Hohenwallner from the University of Vienna.
The research includes studies with stem cells, carried out by Dominik Egger of the Institute of Cell and Tissue Culture Technologies at BOKU Vienna. In addition, the programme “Lipid Data Analyzer” for gangliosides was modified along with researchers from the University of Graz, Institute of Pharmaceutical Sciences.
Surgical tissue waste as samples
For the study, the scientists examined tissue samples taken from medical waste. First, the so-called mesenchymal stem cells were extracted from the tissue and allowed to develop into bone, cartilage, and fat cells. In the course of the investigation, the biggest number of gangliosides were discovered to date.
Additionally, gangliosides were found as possible markers to differentiate the various cell types at the molecular level. Based on automated data analysis, the researchers present a way to thoroughly quantify and structurally define the gangliosides for the first time.
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