Fibrinogen, the precursor of the blood clot matrix, preferentially binds to surfaces newly exposed to blood. This simple event is the foundation for such seemingly diverse events as the thrombosis of blood vessel grafts and the thrombotic complications of atherosclerosis. Fibrinogen adsorption is dictated by the chemical properties of the surface. In fact, the character of the underlying surface has been established as a major dictator of the properties of the adsorbed fibrinogen film. As an example, fibrinogen adsorbed to an amphophilic surface is more adhesive, than is the protein bound when bound to a purely hydrophobic surface. The investigator proposes that fibrinogen adsorbed to certain surfaces is better suited to participate in other biologically relevant events, notably platelet adherence. Further, with regard to platelet adhesion, granule secretion and the resulting prothrombotic nature of the platelet membrane, the investigator proposes the response of platelets depends on the chemical properties of the surface to which fibrinogen is adsorbed. The platelet response, in turn, is determined by the orientation of fibrinogen molecules at the interface. The particular properties of fibrinogen monolayers that regulate platelet binding and subsequent reactivity will be studied using a model amphophilic surface. Microscopic polystyrenedivinylbenzene beads will be modified with a loosely packed monolayer of phosphatidylcholine (lecithin). These particles provide a convenient and biologically relevant system to investigate surface events of coagulation. Platelet adherence to the model surface will be assessed by direct visualization using phase contrast microscopy, by turbidimetric monitoring of forming bead-platelet aggregates and by fluorescent imaging of platelets. Insight gained from these investigations will further the study of interactions between surfaces, both artificial and natural, and components of blood. Others likely to benefit from information yielded from these studies include those developing synthetic biomaterials for blood contacting roles and those investigating thrombotic complications of atherosclerosis.
| Cook, B C (2001) Reactivity of human platelets with immobilized fibrinogen is dictated by the chemical character of the surface. Thromb Res 104:39-48 |
| Cook, B C; Rudolph, A E; Kurumbail, R G et al. (2000) Directed glycosylation of human coagulation factor X at residue 333. Insight into factor Va-dependent prothrombin catalysis. J Biol Chem 275:38774-9 |
| Cook, B C (1999) A turbidimetric assay for quantitating functional fibrin(ogen) using polystyrene-divinylbenzene microparticles. Anal Biochem 270:83-7 |
