B1 - PUBLICATIONS B1 - RESEARCH B1 - STAFF
     
  
  
       

 

The aim of this proposal is to bridge the gap between the molecular variations (mutations) of vWF and its pathophysiological representations by unraveling the physical properties of vWF in a complex, but physiological relevant, microfluidic environment. vWF can be mechanically activated, as it undergoes a coiled-stretched transition under elevated shear stress. A variety of mutations causing both increased clotting or bleeding disorders are identified.

How these mutations lead to their clinical representation, however, remains entirely unknown. The three stages, activation, adhesion and degradation of vWF and its mutations, will be investigated by systematically building a more and more realistic -fluidic model system. In the first step, the activation, i.e. the force elongation dependence (i.e. the function of state) of vWF will be recorded under various hydrodynamic (shear, stenotic, bifurcated condition) and other (pH, T, ions, drugs etc.) conditions.

The second step, the adhesion, will be monitored in biofunctionalized (membranes, proteins, cells) -fluidic channels. Finally, we will study the degradation of VWF under flow. Complemented by the single molecule nanomechanics of C2 our data will reveal a relation between mutation, physical state and clinical impact of vWF and provide a fundamental understanding of the role of physical forces for the process of primary haemostasis and related disease.

 

        
  
  
 
     
B1 - PUBLICATIONS B1 - RESEARCH B1 - STAFF