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Mechanical and biophysical properties of VWF in single molecule and cell adhesion force experiments

In the first funding period we applied AFM as a new approach to probe the platelet adhesion to VWF, the size distribution of VWF, the unfolding of VWF dimers, and the dynamics of binding of selected VWF domains to other VWF domains and to collagen III and VI. For the second funding period we will gain a detailed understanding of the biophysical functionalities of the VWF protein on the single molecule level by establishing a unique combination of nano-mechanics and computer simulation studies with Netz (B4), and Gräter/Baldauf (C1). According to the main task as to explore the links between the mechanical properties of the mechano-sensitive VWF molecule and its function in the interplay with blood components, we will study the formation of VWF-platelet networks and the impact of pathologic VWF mutations in close collaboration with groups Schneppenheim (A1), Wilmanns (C3) Schneider (A2), Wixforth (B1), Rädler (B3). We will thus extend our investigations to collagen I and IV, integrin mediated adhesion to platelets, and endothelial cells under inflammatory conditions. Furthermore we will directly measure changes in the force signature by stretching VWF and VWF mutants under inflammatory conditions. We expect that the clinical relevance of our findings will aid detecting disease and improve the treatment of VWF patients.

Figure: One of our goals is the investigation of the interactions between VWF and specific ligands in the membrane of platelets. Simultaneous topography and recognition imaging will be applied to achieve a detailed picture of the receptor distribution and single cell force spectroscopy will quantify cellular adhesion forces and energies.

 

 

        
  
  
 
     
C2 - STAFF C2 - RESEARCH C2 - PUBLICATIONS