Interdisciplinary collaboration between SHENC laboratories

  

  Within our interdisciplinary network, we, for example, jointly investigate the physiological relevance of the shear-dependent formation of VWF-platelet networks and the influence of genetic variation of VWF on their formation (Figure 1).  
     
   
 

Figure 1. SHENC networking to investigate the physiological relevance of the shear-dependent formation of VWF-platelet networks (details see below).

A1, A2, B1 and B2 investigate VWF mutants in their capacity for platelet binding, string formation and network formation (Figure 1, red oval) using cone and plate analysis and shear flow assays (A1) and utilize an in-vitro-vascular-system (A2). B1 develops a new generation of in-vitro-vascular-model-system which facilitates mimicking essential features of a) stenosis and b) inflammation. B2 performs 2D and 3D simulations of mixtures of VWF, platelets, and red blood cells in flow to investigate adhesion of VWF and platelets in blood flow, formation of VWF-platelet aggregates, and the development of a primary hemostatic plug. Hydrodynamic studies including single molecule effects and polymer-colloid interactions are performed by B1, B2, B3, B4, C1 and C2 (Figure 1, green). Interaction and binding studies are facilitated and performed by A1, A2, B3, C1, C2 and C3 (Figure 1, blue).

B3 provides binding studies of full-length VWF and VWF fragments with platelets and isolated integrins using fluorescence correlation spectroscopy (FCS) as well as microscale thermophoresis (MST). B4 develops coarse-grained models and estimates the model parameters to predict the VWF large-scale structure and VWF-colloid formation in shear and at surfaces including polymer-polymer bundle formation. Using Atomic Force Microscopy (AFM) coupled Single Molecule Force Spectroscopy (SMFS) C2 investigates the mechanics of VWF dimers. To understand which peptide sequences are involved in network formation C3 will attempt to crystallize single VWF domains and domain clusters. C1 aims to understand the molecular origin of alterations in network formation associated with VWF mutations by molecular modeling and Molecular Dynamics (MD) simulations.