Fibrinogen and Hyaluronan
Early work had shown that acacia (1) or poly(ethylene) glycol (2) enhanced fibrin polymerization. There is no evidence that there is specific binding of acacia, a complex polysaccharide, or poly(ethylene) glycol to fibrinogen it is thought that effect of either material is on the polymerization of fibrin monomer.  While there was some early work suggested an interaction of hyaluronan and fibrin (3,4), it was not until the work of Leboeuf and coworkers (5) that it became apparent that there is a relatively specific interaction between hyaluronan and fibrinogen.  Leboeuf and coworkers (5) studied the binding to fibrinogen of hyaluronan in solution and in solid-phase binding.   The binding is of relatively high affinity (Kd ≈4.5 x108). However, this data was obtained from solid phase binding studies using fibrinogen bound to a glass fiber filter.   Binding studies using hyalunonan bound to Sepharose suggest that the interaction is sensitive to ionic strength with approximately 30% of radiolabeled fibrinogen released at 0.15 M NaCL with an additional 20% released at 0.3 M NaCl.  Lysozyme, a basic protein, was bound less tightly that fibrinogen.  Studies from another laboratory have shown that the binding of lysozyme to hyaluronan is very sensitive to ionic strength (6).   Smaller hyaluronan fragments (MW ≈ 3,000) were less effecting that larger polymers (80 kDa). Subsequent work (7) demonstrated that hyaluronan, as observed with acacia and poly(ethylene) glycol enhanced fibrin polymerization and the quality of the final fibrin product.  In more recent work, Rinaudo (8) showed that the addition of fibrinogen to hyaluronan promotes the non-Newtonian behavior when hyaluronan exceeds  the critical overlap concentration.  It would seem that interaction of hyaluronan and fibrinogen may have a role in the development of fibrosis (9) and that the interaction of fibrinogen and hyaluronan with CD44 receptors may be important in this process (10,11). Raman and coworkers (11) studied the interaction of CD44s, the standard CD44 isoform, and a variant CD44, CD44v, with hyaluronan and fibrin using atomic force microscopy.  Fibrinogen was coupled to the cantilever (12) by chemical crosslinking and the force of interaction measured with a CD44 receptor embedded in phospholipid bilayer.   Raman and coworkers (11) observed that the binding of fibrin with CD44 receptor was tighter than fibrinogen but the binding of hyaluronan with CD44 is at least two orders of magnitude tighter than either fibrin or fibrinogen.

1.  Boyles, P.W., Ferguson, J.H., and Muehlke, P.H., Mechanisms involved in fibrin formation,  J.Gen.Physiol. 34, 493-513, 1951.
2.  Fenton, J.W., 2nd and Fasco, M.J. Polyethylene glycol 6,000 enhancement of the clotting of fibrinogen solutions in visual and mechanical assays, Thromb.Res. 4, 809-817, 1974.
3.  Olesen, E.S., Effect of acid polysaccharides on the fibrinolytic system in guinea pig serum, Acta Pharmacol.Toxicol. 15, 307-315, 1959.
4.  Bergovist, D. and Arfors, K.E., Effect of dextran and hyaluronic acid on the development of postoperative peritoneal adhesions in experimental animals, Europ.Surg.Res. 9, 321-325, 1977.
5.  LeBoeuf, R.D., Raja, R.H., Fuller, G.M., and Weigel, P.H., Human fibrinogen specifically binds hyaluronic acid, J.Biol.Chem. 261, 12588-12592, 1986.
6.  Van Damme, M.P., Moss, J.M., Murphy, W.H., and Preston, B.N., Binding of hyaluronan to lysozyme at various pHs and salt concentrations, Biochem.Int. 24, 605-613, 1991.
7.  LeBoeuf, R.D., Gregg, R.R., Weigel, P.H., and Fuller, G.M., Effects of hyaluronic acid other glycosaminoglycans on fibrin polymer formation, Biochemistry 26, 6052-6057, 1987.
8.  Rinanudo, M. Rheological investigation on hyaluronan-fibrinogen interaction, Int.J.Biol.Macromolecules 43, 444-450, 3008.
 9.  Wright, T.N. and Potter-Perigo, S., The extracellular matrix: an active or passive player in fibrosis?, Am.J.Physiol.Gastrointest.Liver Physiol. 301, G950-G955, 2011.
10.  Svee, K., White, J., Vaillant, P.,  et al., Acute lung injury fibroblast migration and invasion of a fibrin matrix is mediated by CD44, J.Clin.Invest. 98, 1713-1727, 1996.
11. Raman, P.S., Alves, C.S., Wirtz, D., and Konstantopoulos, K., Distinct kinetic and molecular requirements govern CD44 binding to hyaluronan versus fibrin(ogen), Biophys.J. 103, 415-423, 2012.
12.  Sullan, R.M., Churnside, A.B., Nguyen, D.C., Bull, M.S., and Perkins, T.T., Atomic force microscopy ith sub-picoNewton force stability for biological applications, Methods  60, 131-141, 2013.