The fibrin network is a 3-dimensional self-assembled structure where the backbone of the network forms within minutes after the initiation of blood clotting. To fulfil its mechanical task as the scaffold of the clot, it possesses remarkable mechanical properties: fibrin needs to be tough to properly seal wounds in highly variable flow conditions such as in the arteries and veins, yet flexible enough to prevent clot rupture. Here I will show an atomic-force microscopy (AFM)- and a magnetic tweezer- based micro-rheology method to study the local mechanical behaviour of fibrin and blood plasma clots. With these methods we have shown how mechanical properties alter in such pathologic conditions as anti-phospholipid syndrome due to impaired platelet contraction or in autoimmune-linked conditions where fibrinogen gets citrullinated.
Using lateral fibre pulling, a method elaborated by Prof. Martin Guthold and established in Leeds by Dr. Stephen Baker, we found that covalent crosslinking induced by FXIIIa increased fibre toughness. However, the location of crosslinking is of importance: crosslinking on the γ-chain had a more prominent effect while crosslinking on the α-chain leads only to minor, insignificant changes. Interestingly, our recent results using fibrinogen variants with partial and complete absence of the αC-region have also indicated that absence of the αC-region doesn’t lead to major alterations in the mechanical behaviour of fibrin fibres. These results are surprising, as the relatively low, 1-10 MPa low-strain stiffness of fibres was classically explained with the undulation of the unstructured αC-region, while stretching the highly-ordered protofibril backbone should result in stiffness in the GPa range. This led us to a novel model of selective protofibril loading which I will present here.

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**Refreshments will be served at 3:30 pm in the Olin lobby.