Preparation and characterization of fibrinogen‐coated, reversibly adhesive, lecithin/cholesterol vesicles

We have developed a method for producing fibrinogen‐coated, reversibly adhesive, lecithin/cholesterol vesicles. In this method, fibrinogen, which is acylated in the presence of preformed vesicles, spontaneously incorporates into vesicular membranes. The degree of incorporation is a function of the extent of acylation of the protein. Fibrinogen‐coated vesicles aggregate in the presence of thrombin, a consequence of intervesicular fibrin formation. The rate and extent of thrombin‐initiated aggregation depend on the fibrinogen surface concentration. Once aggregated, fibrin‐coated vesicles can be dissociated by plasmin and by agents that disrupt intervesicular fibrin dimerization such as heparin and the tetrapeptide Gly‐Pro‐Arg‐Pro. Fibrinogen‐coated vesicles can be made to bind avidly to the surface of solution phase fibrin matrices and can be incorporated into solution phase fibrin clots. Fibrinogen‐coated vesicles also bind to activated platelets. We propose that fibrinogen‐coated vesicles will have practical applications as biomimetic hemostatic agents and as vehicles for the fibrin‐specific targeting of drugs and other molecules.