How structure defines mechanical behaviour of fibrin (360G-Wellcome-227651_Z_23_Z)

The structure and mechanical properties of fibrin are of key importance in pathologic conditions such as venous thromboembolism, heart attack or ischaemic stroke, as well as in the dissolution of pathologic thrombi. Structure determines the mechanical properties of fibrin, yet the exact structure, especially on sub-fibre level is still not known. Targeting structures playing a key role in fibrin’s mechanical behaviour offers a promising route to the treatment of pathologic conditions and reveal details of diagnostic importance. My very recent data provide strong evidence for the structural and mechanical role of the αC-region. This has led me to a novel model, where highly branching protofibrils are the key load-bearing elements and the αC-region is important for structural integrity. This new model will provide a fresh perspective and could explain the unique mechanical properties of fibrin. In the scope of this award, I will do a broad investigation of both structure and mechanical properties, from molecule to network level. I will bring together all the results to provide a comprehensive model of the structure of fibrin, provide evidence how structure determines mechanical properties of fibrin and investigate how this new understanding can be used to target treatments for pathological conditions.