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.
DeAnglis
A P
AP
Department of Pathology, University of Cincinnati Medical Center, OH 45267, USA.
Retzinger
G S
GS
D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002784:Cholesterol / Q000737:chemistry*; D002850:Chromatography, Gel; D016503:Drug Delivery Systems; D005337:Fibrin / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry*; D006801:Humans; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000737:chemistry*; D009764:o-Phthalaldehyde
D010713:Phosphatidylcholines; D009764:o-Phthalaldehyde; D005337:Fibrin; D005340:Fibrinogen; D002784:Cholesterol