The Fibrinogen Molecule: Its Size, Shape, and Mode of Polymerization

Hall, Cecil E.; Slayter, Henry S.

doi:10.1083/jcb.5.1.11

Cited by 536 publications

(218 citation statements)

References 19 publications

(29 reference statements)

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“…the computed axial ratio offibrinogen was reduced from ! 8:1 to 5:1 (327,344), a result that is compatible with electron micrographs (103) of this protein. Further, the view that urea denaturation of proteins leads to increased asymmetry (due to unfolding ofpolypeptide chains) was altered to one in which the protein swells (almost isotropically) (325).…”

Section: Early View Of Proteinssupporting

confidence: 71%

Protein structure and function, from a colloidal to a molecular view

Scheraga

1984

Carlsberg Res. Commun.

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Section: Early View Of Proteinssupporting

confidence: 71%

Protein structure and function, from a colloidal to a molecular view

Scheraga

1984

Carlsberg Res. Commun.

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“…The parent protein, fibrinogen, is an elongated, sausage-shaped dimeric molecule with symmetry around a central globular domain (2)(3)(4)(5)(6). Cleavage and removal of the small peptides-fibrinopeptide A and later B-from fibrinogen by the enzyme thrombin expose specific binding sites (''knobs'') on fibrin that allow binding to corresponding regions (''holes'') on neighboring fibrin molecules (7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

Ultrathin self-assembled fibrin sheets

Falvo

Millard²,

Eastwood

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Fibrin polymerizes into the fibrous network that is the major structural component of blood clots and thrombi. We demonstrate that fibrin from three different species can also spontaneously polymerize into extensive, molecularly thin, 2D sheets. Sheet assembly occurs in physiologic buffers on both hydrophobic and hydrophilic surfaces, but is routinely observed only when polymerized using very low concentrations of fibrinogen and thrombin. Sheets may have been missed in previous studies because they may be very short-lived at higher concentrations of fibrinogen and thrombin, and their thinness makes them very difficult to detect. We were able to distinguish fluorescently labeled fibrin sheets by polymerizing fibrin onto micropatterned structured surfaces that suspended polymers 10 m above and parallel to the cover-glass surface. We used a combined fluorescence/atomic force microscope system to determine that sheets were Ϸ5 nm thick, flat, elastic and mechanically continuous. Video microscopy of assembling sheets showed that they could polymerize across 25-m channels at hundreds of m 2 /sec (Ϸ10 13 subunits/s⅐M), an apparent rate constant many times greater than those of other protein polymers. Structural transitions from sheets to fibers were observed by fluorescence, transmission, and scanning electron microscopy. Sheets appeared to fold and roll up into larger fibers, and also to develop oval holes to form fiber networks that were ''preattached'' to the substrate and other fibers. We propose a model of fiber formation from sheets and compare it with current models of end-wise polymerization from protofibrils. Sheets could be an unanticipated factor in clot formation and adhesion in vivo, and are a unique material in their own right.clot ͉ fiber ͉ monomolecular sheet ͉ network ͉ thrombus B ecause of the central role of fibrin in the clotting of blood during wound healing and in the formation of pathogenic vascular thrombi, the polymerization of fibrin has been actively studied since the mid-19th century (1). The parent protein, fibrinogen, is an elongated, sausage-shaped dimeric molecule with symmetry around a central globular domain (2-6). Cleavage and removal of the small peptides-fibrinopeptide A and later B-from fibrinogen by the enzyme thrombin expose specific binding sites (''knobs'') on fibrin that allow binding to corresponding regions (''holes'') on neighboring fibrin molecules (7-11). Fibrin can then self-associate to form elongated, sometimes twisted, often highly branched fibers and fiber networks that, together with platelets and blood cells, form clots in response to vascular injury (1,(12)(13)(14)(15). Fibrin fibers are elastic and adhesive and show very high extensibility (16,17). Recent studies suggest that these properties derive, at least in part, from the properties of the fibrin molecule itself (18-21). Exhaustive studies of fibrin polymerization in vitro have been carried out with purified components since the 1940s (e.g., 22, 23), but several details of fibrin assembly into fibers and fibe...

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“…Despite intensive biochemical and biophysical investigation (17), many details concerning this reaction are obscure, although it has long been recognized that the final clot structure is greatly influenced by the biochemical milieu, particularly with respect to pH and ionic strength (18,19), in which clotting occurs. Moreover, electron microscopic study has yet failed to provide an entirely satisfactory basis for clot structural configuration explainable on a molecular basis (14,15,20). Nevertheless, clots formed in thin layer sheet from either purified fibrinogen or from plasma in a milieu of defined physicochemical properties exhibit, when examined by electron microscopy, a consistent structural pattern.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the development of two ingenious theories (15,20,21), there is uncertainty as to the precise molecular arrangement by which fibrin monomer units polymerize to produce cross striations with regular periodicity. These striations, an obvious and striking feature in technically adequate micrographs, would appear to represent the molecular subunit of structure; adequate explanation for their appearance on the basis of molecular arrangement and alignment would greatly facilitate interpretation of micrographs.…”

Section: Discussionmentioning

confidence: 99%