Fibrin Formation, Structure and Properties

  • John W. WeiselEmail author
  • Rustem I. Litvinov
Part of the Subcellular Biochemistry book series (SCBI, volume 82)


Fibrinogen and fibrin are essential for hemostasis and are major factors in thrombosis, wound healing, and several other biological functions and pathological conditions. The X-ray crystallographic structure of major parts of fibrin(ogen), together with computational reconstructions of missing portions and numerous biochemical and biophysical studies, have provided a wealth of data to interpret molecular mechanisms of fibrin formation, its organization, and properties. On cleavage of fibrinopeptides by thrombin, fibrinogen is converted to fibrin monomers, which interact via knobs exposed by fibrinopeptide removal in the central region, with holes always exposed at the ends of the molecules. The resulting half-staggered, double-stranded oligomers lengthen into protofibrils, which aggregate laterally to make fibers, which then branch to yield a three-dimensional network. Much is now known about the structural origins of clot mechanical properties, including changes in fiber orientation, stretching and buckling, and forced unfolding of molecular domains. Studies of congenital fibrinogen variants and post-translational modifications have increased our understanding of the structure and functions of fibrin(ogen). The fibrinolytic system, with the zymogen plasminogen binding to fibrin together with tissue-type plasminogen activator to promote activation to the active proteolytic enzyme, plasmin, results in digestion of fibrin at specific lysine residues. In spite of a great increase in our knowledge of all these interconnected processes, much about the molecular mechanisms of the biological functions of fibrin(ogen) remains unknown, including some basic aspects of clotting, fibrinolysis, and molecular origins of fibrin mechanical properties. Even less is known concerning more complex (patho)physiological implications of fibrinogen and fibrin.


Fibrin formation Fibrin structure Fibrin properties Fibrinogen composition α-Helical coiled-coil Blood clot Fibrin polymerization Clot mechanical properties Molecular mechanisms of fibrinolysis Modulation of clot structure 


FpA and FpB

fibrinopeptides A and B






Asn-X-Ser or Asn-X-Thr






tissue-type Plg activator



Some of the authors’ work mentioned here was supported by NIH grants NHLBI HL090774 and UO1HL116330, and NSF grant DMR1505662. We thank Drs. Oleg V. Gorkun and Lubica Rauova for careful reading of the manuscript and helpful suggestions.


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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Cell and Developmental BiologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

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