Can dynamic remodelling of fibrin fibres under load account for the remarkable mechanical properties of blood clots?

To fulfil its physiological role as the scaffold of blood clots, fibrin has large extensibility and strain stiffening behaviour, which make it deformable but tough at the same time. Yet fibrin's exact structure, especially on the sub-fibre level, is unknown.

Current models do not explain many of its properties, including its elastomeric properties with strains of up to an incredible 400% observed.

Recent data points to the possibility of dynamic remodelling of the fibrin network, the structure is not static when load is applied as assumed, but responds with bonds breaking and reforming. Some of this can be attributed to catch-slip bonds.

This project will utilise Fluctuating Finite Element Analysis (FFEA), an in-silico model to test the mesoscopic interactions of protofibrils as they build to network level structures.

This will inform and guide experimental in vitro methods that will test the mechanical behaviour during formation and extension of fibrin across multiple length scales: from molecular through fibre up to network level.

We will apply the latest techniques established in our lab over the last few years, in passive particle tracking micro-rheology with high speed cameras, with active micro-rheology using magnetic tweezers, and the measurement of single fibres using AFM lateral pulling. Dynamical remodelling will be measured using novel fluorescence techniques at the same time as manipulation with AFM.