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Biomaterials Tutorial
Fibrinogen
M. Jeanette Stein
University of Washington Engineered Biomaterials
Fibrinogen (Fg) is a 340 kDa (~3,000 amino acid) member of the adhesive protein family, whose members also include fibronectin (Fn) and von Willebrand factor (vWF). Primarily located in the blood plasma (at a concentration of 200-400 mg/dl), it is a dimeric protein molecule; each half-molecule contains three non-identical peptide chains (a, b, g) as shown in Figure 1. Unlike Fn and vWF, which are believed to have a role in platelet substratum interactions, Fg is the most important protein. It supports platelet-platelet aggregation, which leads to blood clotting through coagulation. In this role, fibrinogen coordinates the Ca+-dependent bridging of adjacent platelets in platelet-platelet interactions.
In contrast to other blood plasma proteins, Fg appears to play a major role in the inflammatory response, in addition to its role in blood coagulation. Decades of protein adsorption work has revealed that Fg immediately adsorbs to most biomaterials upon entry into the body. The amount adsorbed increases with time until the material is coated in protein. When this protein adsorbs onto a foreign material, it denatures and unfolds, revealing components which are responsible for the recruitment of a number of phagocytic cells ( i.e., mobile immune system cells, like macrophages or neutrophils, that are designed to take up and engulf particles and microorganisms by phagocytosis). If the implant is sufficiently large, then this usually results in the build-up of a hard fibrous encapsulation which typically leads to the loss of implant function.

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Figure 1. Diagram of the gross structure of a fibrinogen molecule. |
References:
- Hall CE, Slayter HS. The fibrinogen molecule: Its size, shape, and mode of polymerization. J Biophys & Biochem Cytology 1959; 5 (1): 11-15.
- Plow EF, Marguerie G, Ginsberg M. Fibrinogen, fibrinogen receptors, and the peptides that inhibit these interactions. Chem Pharma 1987; 36 (23): 4035-4040.
- Phillips DR, Charo IF, Parise LV, Fitzgerald LA. The platelet membrane glycoprotein IIb-IIIa Complex. Blood 1988; 71 (4): 831-843.
- Rao SPS, Poojary MD, Elliott BW, Melanson LA, Oriel B, Cohen C. Fibrinogen structure in projection at 18 ? resolution. K Mol Biol 1991; 222: 89-98.
- Biomaterials science: An introduction to materials in medicine. Ratner BD, Hoffman AS, Schoen FJ, Lemons JE, editors. San Diego, CA: Academic Press, 1996.
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