(15h) Fibronectin Increases the Rate of Fibrin Clot Polymerization and Alters Matrix Morphology

Plasma fibronectin is essential for the formation of thrombi, a provisional fibrin matrix that arrests bleeding in damaged tissues.  The initial rate of fibrin polymerization and the steady state absorbance for fibrin clots with varying concentrations of full-length plasma fibronectin were monitored via light absorbance.  At higher fibrin concentrations, the initial rate of polymerization and steady state absorbance increased with increasing fibronectin concentration. Similar behaviors were seen at a lower fibrin concentration, but less pronounced.  Three dimensional fibrin clot structure was examined by confocal microscopy z-stacks. Fibrin clots formed in the absence of fibronectin appeared to have straight, pin-like fibers and clots formed with high concentrations of fibronectin had finer, densely packed fibers.  When incubated in denaturing buffer, fibronectin was not released from the fibrin clot, but the entire clot was soluble in reducing buffer; indicating possible disulfide bonding between fibrin and fibronectin.  These results provide insight into the mechanism in which thrombi form in vivo and indicate that plasma fibronectin could be a useful target for clot destabilizing therapeutics.