From Single Molecules to Collective Phenomena - The Origin of VWF-Induced Collective Networks

• Applicant: Professor Dr. Achim Wixforth
• Subject Area: Biophysics
• Term: from 2011 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 172540668

The aim of this proposal is to take the next step in understanding primary hemostasis: from single molecules to collective phenomena of VWF induced blood clotting. In the first period, we were able to demonstrate, that under whole blood conditions and high shear rates, VWF initiates the formation of large reversible aggregates consisting of several 100-1000 VWF fibers and platelets. If not regulated, such aggregates when forming in vivo would have devastating consequences. Indeed data from our group and our clinical collaborators (A1 and A2) strongly indicate that pathological aggregate formation in mutant forms of VWF correlate with an increased rate of heart attacks. How the properties of the biopolymer VWF, however, relate to the formation of these aggregates and how these aggregates may be suppressed/enhanced in vivo remains entirely unknown. Physical and (bio)chemical aspects controlling aggregate formation while mimicking stenotic and inflammatory conditions will be investigated. Further, although critical for thrombus formation, the interaction of the aggregates with the vessel wall is commonly neglected in in-vitro model systems, mainly due to the lack of proper techniques. A new generation of in-vitro models with "active" walls will be designed, which allows to mimic inflammatory conditions by controlling clusters of receptors. Complemented by single molecule experiments and mesoscopic theoretical models our results will provide an extensive fundamental understanding of the relation between biological, chemical and physical aspects of VWF induced aggregate formation and it´s relation to primary haemostasis and the risk of thrombosis in heart attack and stroke.

• DFG Programme: Research Units
• Subproject of: FOR 1543: Shear Flow Regulation of Hemostasis - Bridging the Gap between Nanomechanics and Clinical Presentation
• International Connection: USA
• Cooperation Partner: Professor Dr. Matthias F. Schneider