CDT Postgraduate Studentship in Healthcare Innovation (RCUK Digital Economy Programme grant number EP/G036861/1)
Atomic scale modelling of the Endothelial Glycocalyx in Physiological Flow
In this work we investigate the mechanical way in which the shear stress acting on the endothelial wall is transmitted to the cytoskeleton, causing a biochemical response. For this purpose, we use atomistic-scale molecular simulation to construct a representative model of the endothelial glycocalyx as well as its surrounding environment, in equilibrium (diffusion) and non-equilibrium (flow) conditions. This is the first time non-equilibrium molecular dynamics is used to simulate the endothelial glycocalyx. We discuss this approach in the context of other methods and related work in the field and present preliminary results of the current model, as well as validation for this work based on previous models and experimental results from the literature. Important differences between the mechanical behavior of the glycocalyx model in equilibrium and non-equilibrium states are highlighted, in terms of flow induced deformation (bending of the molecules, elongation, and glycosidic linkage angle rotations).
We envisage that by a thorough understanding of the mechanical properties of the complex carbohydrates that constitute the endothelial glycocalyx layer, we can unfold its pivotal role in the process of mechanotransduction.