Fibrin Formation, Structure and Properties

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Fibrin Formation, Structure and Properties
John W. Weisel and Rustem I. Litvinov
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, 
Philadelphia, PA, USA
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

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