Rheometrical and molecular dynamics simulation studies of incipient clot formation in fibrin-thrombin gels: An activation limited aggregation approach

A rheometrical investigation of incipient clots formed in fibrin-thrombin gels is reported in which the Gel Point (GP) is characterised by frequency independence of the loss tangent in small amplitude oscillatory shear measurements over a wide range of thrombin concentration. Values of the fractal dimension (D_f) of the GP network calculated from measurements are consistent with those reported in simulations of diffusion limited cluster-cluster aggregation (DLCCA) and reaction limited cluster-cluster aggregation (RLCCA), but differ insofar as the values of D_f calculated from the present experiments increase progressively with a reduction in gel formation time. A molecular dynamics simulation (MDS) of systems of rod-like particles was designed to (i) test the hypothesis that the presence of an activation profile in a cluster aggregation model could account for the trend of D_f as a function of gel formation time observed experimentally in fibrin-thrombin gels and whole heparinised blood without recourse to the inclusion of fibrinogen-specific interactions; and (ii) to explore the effect of monomer activation kinetics on the microstructure of fractal clusters formed in systems of rigid rod-like particles. The results identify two possible mechanisms for the increase in D_f as the gel formation time decreases, both being a consequence of altering the evolution of the clustering dynamics by a process referred to herein as activation limited aggregation (ALA). This ALA-based MDS substantiates the experimental findings by confirming the trend evident in the formation of incipient clots in fibrin-thrombin gels and in whole heparinised blood. A mechanism for ALA involving the aggregation of pre-GP sub-clusters is proposed.