Twisting of fibrin fibers limits their radial growth.

Abstract

Electron microscopy of freeze-dried, shadowed fibrin fibers has demonstrated that these structures are twisted. The pitch and radius of many fibers were measured from the micrographs. Although there is some variability, the average pitch of 1930 ± 280 (SD) nm is independent of radius. The distribution of observed radil of fibers assembled in vitro is highly skewed, suggesting that individual fibers grow to a maximum radius of about 50 nm, except when both pH and ionic strength are high; fibers aggregate to form thicker fiber bundles under some conditions. The observed twisting may be responsible for limiting the lateral growth of individual fibers. Protofibrils near the surface of a twisted fiber are stretched relative to those near the center. Consequently, the degree to which a protofibril can be stretched limits the radius of a fiber; protofibrils can be added to a growing fiber until the energy required to stretch an added protofibril exceeds the energy of binding. These properties of assembly arise directly from the intrinsic twist of the fibrinogen molecule determined from structural evidence. Simple geometric considerations lead to conclusions regarding the locations of the binding sites for assembly of the protofibril and the flexibility of the fibrin molecule.The physical properties of blood clots are determined to a large extent by properties of fibrin fibers, such as diameter, degree ofaggregation, stability, and resistance to proteolysis. Fibrinogen is the soluble precursor of the fibrin clot. It has a molecular weight of 340,000 and is made up of three pairs of polypeptide chains, (AaBI3y)2. The molecule is 45 nm in length and consists of globular domains connected by rodlike, a-helical coiled-coil domains (1, 2). All amino termini are linked together in the central domain, the disulfide knot.The carboxyl-terminal ends of the BP and y chains form the proximal and distal end domains, respectively. The carboxylterminal ends of both of the Aa chains appear to interact to form a domain adjacent to the central domain.Fibrin fibers with an axial repeat of 22.5 nm form from fibrinogen upon removal of the fibrinopeptides by thrombin. Cleavage of the fibrinopeptides in the central domain of the molecule exposes binding sites that are complementary to sites always present at each end of the molecules (1). These specific interactions result in the half-staggering of molecules to form two-stranded protofibrils, which then aggregate laterally to yield fibers. The characteristic 22.5-nm band pattern seen in electron micrographs of fibrin fibers indicates that the protofibrils align in register axially. Electron micrographs of cross sections offibers indicate that the side-to-side packing of protofibrils is disordered, although the average distance between neighboring protofibrils exhibits some regularity (ref. 3; J.W.W. and J. G. White, unpublished data).The diameter of fibrin fibers is an important component in determining the physical properties of the fibrin clot. Diameters of fibers from clots made un...

Ultrathin self-assembled fibrin sheets

“…Tension within fibrin fibers has been attributed to an inherently helical association of monomers as they bind to lateral faces of a protofibril (36). This association was suggested to produce tension as the protofibril shortens to allow favorable binding of new monomers, and also causes an intrinsic twist to the fiber.…”

The Molecular Weights, Mass Distribution, Chain Composition, and Structure of Soluble Fibrin Degradation Products Released from a Fibrin Clot Perfused with Plasmin

“…First, fibrinogen and fibrin protofibrils have been shown to possess intrinsic flexibility (52), and it is reasonable to conclude that fibrin degradation products will also possess intrinsic flexibility. The amount of flexibility (movement) of a fibrin degradation product, relative to the long axis of the protofibril, is related to its length such that longer protofibrils possess greater flexibility.…”

Aβ delays fibrin clot lysis by altering fibrin structure and attenuating plasminogen binding to fibrin

“…Fibrin fibers are known to be twisted, and the stretching of twisted fibrin strands determines the limit of fiber thickness. 41 A␤-intercalated fibrin fibers ( Figure 5E-F) may be less flexible and could therefore yield thinner fibers arranged in a tighter network.…”