Fibrinogen Structure – Function
The heart of Fibriant™’s science and technology is fibrinogen, a soluble blood protein that can rapidly be converted into an insoluble three-dimensional fibrin network. In vivo this conversion takes place as a result of tissue injury and / or blood vessel damage that triggers the coagulation cascade which ultimately leads to the generation of thrombin. Active thrombin releases small peptides from fibrinogen, activating sites by which the now fibrin monomer molecules can interact with each other and assemble into fibrin polymer strands, which subsequently become integrated into the insoluble three dimensional fibrin network (see Fig 1)
Figure 1: On the left a schematic representation of thrombin induced fibrin formation is shown. On the right electron microscopy pictures of individual fibrinogen molecules before activation (top) and a fibrin polymer network after polymerization (bottom) are shown.
The fibrin network is predominantly known for its important role in blood clotting where it provides a scaffold for platelets and other blood cells to form a mature haemostatic plug that seals the injury to the vessel wall, preventing further blood loss and initiating subsequent tissue healing. Recent scientific evidence demonstrates that the structure of the fibrin network plays an important role in tissue repair, remodelling and regeneration by supporting cell migration and influencing cellular phenotype.
Fibrin and fibrinogen also appear to regulate processes such as wound healing, tissue re-modelling, cell differentiation, inflammation and immune response. Elucidation of the exact mechanisms involved in these non-haemostasis functions of fibrin and fibrinogen could identify them as therapeutic targets to treat or prevent diseases in which one or more of these (patho) physiological processes play a role.
The fibrinogen molecule occurs in vivo in many different forms and shapes. Each of these fibrinogen variants has unique functional properties and can form fibrin matrices with different structural and functional characteristics (see Fig 2). Several of these fibrin polymers have interesting properties which can be explored for unique healthcare applications.
Electron microscopic images of fibrin matrices formed form different variants of fibrinogen. The 3D fibrin matrices differ in diameter of individual fibers, pore size of the network, number of branch points and have different biomechanical properties.