Establishing Platelet FXIII-A-Fibrin Interactions via Super Resolution Microscopy

The formation of blood clots, also known as the blood coagulation cascade, is a complicated process driven by cascading enzyme interactions that serves to stop blood from leaving blood vessels at the site of injury while maintaining constant blood flow within the body. It is known that bleeding disorders such as hemophilia, von Willebrand disease, and conditions such as deep vein thrombosis are caused by an excess or lack of proteins and enzymes within the cascade known as factors. Clotting results in the formation of fibrin polymers from fibrinogen protein in plasma. Factor 13-A (FXIII-A) induces cross-linking between individual fibrin fibers to enhance the mechanical strength and stiffness of a blood clot. FXIII-A is expressed on the surface of activated platelets, which is responsible for pulling the fibers and contracting the clot. However, it is unknown how individual fibrin fibers will interact with FXIII-A on platelet surfaces during fibrin formation and clot contraction. The aim of this research is to elucidate how FXIII-A density and distribution on the platelet surface will impact interactions with individual fibrin fibers through novel super-resolution microscopy methods known as 4X and 10X expansion microscopy.