While many recent clinical studies associate cardiovascular diseases with increased levels of Fibrinogen (Fg) in the blood stream, comparatively very few basic
science investigations are concerned with the influence of Fg concentration variability on its main functional properties, i.e. on clot formation, mechanical properties and lysis. The objective
of this PhD is to characterize, understand and model how fibrin grows from fibrinogen (kinetics and ultrastructure), resists to flow (multi scale structure, linear and nonlinear rheology) and
then dissolves (kinetics and ultrastructure), first in normal conditions then in conditions simulating thromboembolic diseases.
The main expected breakthrough is the understanding of several very important issues concerning thrombosis including thrombus resistance to lysis and thrombus break up.
PI: François Caton
Co-PI: Benoit Polack
PhD: Xabel Garcia Gonzalez
PhD defense: 14th of decembre 2017
Fibrin clot formation is one of the major processes leading to blood clotting. It involves the polymerization of fibrin monomers into a network of fibrin fibres. This network controls the mechanical properties of the clot and serves as a skeleton for wound healing. Environmental factors (pH, concentration, ...) have been proved to influence polymerization, however the role of fibrinogen composition on the structure of fibrin remains unexplored. This aspect might be important for the case of cardiovascular pathologies, which present abnormal fibrin structures. We have determined the relation between different sources of fibrinogen with the nano-and micro-metric structural and mechanical properties of fibrin clots. The composition in co-purified proteins of the fibrinogens has no significant importance, however the polydispersity profile controls the multiscale properties of fibrin. Indeed, x-ray scattering, multi-wavelength spectrophotometry and
confocal microscopy measurements have proved that fibres from monodisperse fibrinogens are quasi-crystalline, straight and rigid. Fibres from polydisperse fibrinogens are less organised, curbed and less rigid. Finally, the mechanical properties of fibrin showed that the response of clots to deformation, as well
as the scenarios of rupture are closely related to the structure, and consequently related to the profiles of polydispersity. This opens outstanding perspectives in many fields such the optimisation of fibrinogen’s use on dysfibrinogenemies or haemorrhage, tissue regeneration or the understanding between the abnormal structure of clots and cardiovascular diseases.
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