UCL Institute of Health Informatics


DPhil awarded to IHI researcher

24 January 2017

Congratulations to Maria Pikoula, Clinical Data Systems Architect in the IHI's Data Lab who has been awarded a PhD with a project entitled, "Multiscale modeling of the endothelial glycocalyx in physiological flow: A molecular dynamics approach".


The luminal surface of endothelial cells which line the vasculature is coated with a layer of membrane-bound macromolecules of mainly carbohydrate as well as protein nature, collectively described as a glycocalyx, from the greek meaning “sweet husk/covering”. Experiments have consistently revealed the pivotal role of the endothelial glycocalyx layer in vasoregulation and the layer’s contribution to mechanotransduction pathways. However, the exact mechanism by which the glycocalyx mediates and interprets fluid shear stress remains unknown. 


This study employs atomic-scale molecular simulation with the aim of investigating the conformational and orientation properties of the highly flexible components of the glycocalyx and their suitability as transduction molecules under hydrodynamic loading. To this aim, two molecular dynamics systems were constructed. 

The first system focused on the impact of flow on a tethered, branched, oligosaccharide. The second system consisted of charged and non-charged heparan sulfate, a component found in large quantities in the endothelial glycocalyx layer. Systems of paired heparan sulfate strands were investigated under conditions of increasing proximity, which is the expected effect of compression of the layer under the effect of flow. 


Results of the “glycan in flow” model suggest that shear flow through the layer can have an impact on the conformational properties of saccharide-decorated transmembrane proteins, thus probably acting as a mechano-transducer. 

Results of the heparan sulfate model suggest that areas of locally high charge density within the glycocalyx, generally areas of high sulfation, are characteristically more resistant to compression than non- sulfated areas. The sulfation mix therefore emerges as an important determinant of the glyocalyx layer mechanical properties.