Effects of semi-dilute actin solutions on the mobility of fibrin protofibrils during clot formation

Abstract

Low concentration of actin filaments (F-actin) inhibit the rate and extent of turbidity developed during polymerization of purified fibronogen by thrombin. Actin incorporates into the fibrin clot in a concentration-dependent manner that does not reach saturation, indicating nonspecific trapping of actin filaments in the fibrin network. Actin does not retard activation of fibrinogen by thrombin, but rather the alignment of fibrin protobirils into bundles which constitute the coarse clot. In contrast, equivalent F-actin concentrations have little or no effect on the turbidity of plasma clots. The difference is attributed to the presence of a plama protein, gelsolin, that severs actin filaments. Purified gelsolin greatly reduces the effect of F-actin on the turbidity of a pure fibrin clot and decreased the fraction of actin incorporated by the clot. A calculation of the extent to which the gelsolin concentrations used in these experiments reduce the fraction of actin filaments which are long enough to impede each other's rotational diffusion indicates that it is the overlapping actin filaments which retard the association of fibrin protofibrils. The finidings suggest that one role for the F actin depolymerizing and particularly actin severing activities in blood is to prvent actin filaments released by tissue injury from interpreting with the formation of coarse fibrin clots.