Role of lipids in disease, glycosphingolipids and the external surface of cells

Chemical structure of GM3, a monosialated ganglioside.

Chemical structure of GM3, a monosialated ganglioside that is precursor to more complex members of its metabolic family (GD3 and GT3, also involved in signaling processes of cancer cells). The left structure is adapted from Fig 1 in Groux-Degroote, ChemBioChem 18 (13): 1146-1154


Current cancer research is devoted to advance diagnostic tools for early detection and monitor treatment progress. Latest research in this area is focused in developing biomechanical methods to measure cell rigidity or lipidomics as markers for cancer. 

This field is rapidly advancing as the involvement of lipids in cell metabolism and in several diseases is discovered. For example, sphingolipids and cholesterol have been identified in the past years as key modulators of drug permeation and even responsible for development of drug resistance. Glycosphingolipids or gangliosides are a special group of molecules generally present in small percentages in the outer leaflet of the plasma membrane in healthy cells, but overexpressed in the exterior of cancer cells, making them good candidates as diagnostic or therapeutic targets. A key characteristic of these lipids is their bulky headgroup, formed by carbohydrates ranging from a single sugar to multiple covalently attached sugar molecules arranged in linear of branched conformations. The diversity and complexity of this lipid headgroups remains to be fully understood at the molecular level. We study model gangliosides to identify inter and intra-molecular interactions of these lipids at different concentrations in model membranes. Our goal is to provide fundamental understanding on the effect of glycosylation on the external surface of the cell, and examine the interaction of small molecules at the membrane interface that have potential applications for imaging techniques.