Effects of Plasma Fxiii on Clot Structure and Cellular Fxiii on Fibrin Gel Stiffness

Blood clot is an essential component in the understanding of how our body reacts toinjury. These blood clots are made up of various components but to understand this study, we have to focus on FXIII. FXIII is a pro-transglutaminase, that is, it is an enzyme which acts as a catalyst for chemical reactions between molecules and is most known for its crosslinking properties.. Although the role of FXIII present in plasma is well studied and seen to inhibit fibrinolysis, its effect on platelet-fibrin interaction and clot structure is not understood. Similarly, there is a need to understand cellular FXIII and its role. To study effects of FXIII on clots, FXIII was inhibited with T101 and based on fluorescence microscopy on platelet aggregates and fibrin, it was observed that the platelet aggregate volume reduced and fibrin length increased significantly. We demonstrate effects of FXIII which is present on the surface by a microparticle conjugation model. This model shows that the presence of FXIII can influence the clot structure by binding with fibrin. FXIII conjugated microparticles showed higher affinity towards firbin and increased fibrin-microparticle interactions. Further, to understand the effects of cellular FXIII on clot stiffness, THP-1 cells were stimulated with IL-10 which resulted in increased storage modulus. To summarize, our studies provide evidence that proves FXIII affects the clot structure and cellular FXIII can alter the mechanical properties of the fibrin clot