Mathematical modeling to understand the role of bivalent thrombin-fibrin binding during polymerization
Fig 2
Schematic of the four main stages in the polymerization model.
(A) Thrombin forms fibrin I and fibrin II monomers. Thrombin (yellow shape) binds the the E-domain of fibrinogen (purple with blue and green dots), cleaving FpA (green dots), which converts fibrinogen into fibrin I (purple with blue dots). Thrombin binds to the E-domain to cleave FpB (blue dots), converting fibrin I into fibrin II (purple with no dots). (B) Fibrin I and II bind together forming half-staggered chains called oligomers. Fibrin I and II also bind to existing oligomers, increasing them in length. When an oligomer reaches a critical length (11 monomers in length for this study), it becomes a protofibril. (C) Protofibrils aggregate laterally, forming fibers, which are cable-like bundles of protofibrils. Additional protofibrils can bind to an existing fiber, increasing its diameter. (D) As protofibrils and fibers are formed, FpB continues to be cleaved from fibrin I that is incorporated into protofibrils and fibers. Fibrin I is considered to have a limiting effect of lateral aggregation, slowing the process as the ratio of fibrin I to fibrin II increases. The bottom of the figure shows a diagram of the model flow, particularly how key components of the model are connected and which estimated parameters affect each component. The colors in the flow diagram match those in the schematics above.