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Biomedical subjects

M W Mosesson

Publications and source records attributed to M W Mosesson.

At least 73 records · Page 4Linked to original sources
PubMed1991

Evidence for thrombin enhancement of fibrin polymerization that is independent of its catalytic activity.

Inhibition of thrombin proteolysis of fibrinogen with D-phenylalanyl-L-propyl-L-arginine chloromethyl ketone (PPACK) results in irreversible inactivation of the thrombin catalytic site, but the PPACK-inhibited thrombin, through its exosite, retains its ability to bind to fibrinogen or fibrin. Hirudin inactivates thrombin at the catalytic site and also inhibits thrombin exosite binding to fibrin or fibrinogen. PPACK or hirudin was added to a clotting mixture of fibrinogen and active thrombin (enzyme-to-substrate ratio = 1:400 at ionic strength of 0.14; 1:800 at ionic strength of 0.09) before the onset of gelation. Subsequent fibrin assembly was evaluated by turbidity measurements at 350 nm and by determining the fibrin and fibrinogen content of the clots that ultimately formed. Polymerization rates and the fibrin-fibrinogen content of the clots that formed were greater in the PPACK-inhibited system than in the hirudin-inhibited system, and the effect was amplified at the lower ionic strength. PPACK-thrombin also promoted the polymerization of native or prepared mixtures of fibrin and fibrinogen. The results suggest that in addition to its well-recognized role in the proteolytic conversion of fibrinogen to fibrin, thrombin functions through exosite binding to fibrin as a cofactor in fibrin polymerization by accelerating fibrin clot assembly.

Amino Acid Chloromethyl Ketones↗
PubMed1990

The polymerization and thrombin-binding properties of des-(B beta 1-42)-fibrin.

Multiple factors affect the thrombin-catalyzed conversion of fibrinogen to fibrin, including: fibrinopeptide (FPA and FPB) release leading to exposure of two types of polymerization domains ("A" and "B," respectively) in the central portion of the molecule, and exposure of a noncatalytic "secondary" thrombin-binding site in fibrin. Fibrinogen containing the FPA sequence but lacking the B beta 1-42 sequence ("des-(B beta 1-42)-fibrinogen"), was compared to native fibrinogen (containing both FPA and FPB) to investigate the role played by B beta 1-42 in the polymerization of alpha-fibrin (i.e. fibrin lacking FPA), to compare reptilase and thrombin cleavage of FPA from fibrinogen, and to explore the location and function of the secondary thrombin-binding site. Electron microscopy of evolving polymer structures (mu, 0.14; pH 7.4) plus turbidity measurements, showed that early thin fibril formation as well as subsequent lateral fibril associations were impaired in des-(B beta 1-42)-alpha-fibrin, thus indicating that the B beta 1-42 sequence contributes to the A polymerization site. Reptilase-activated des-(B beta 1-42)-alpha-fibrin polymerized even more slowly than thrombin-activated des-(B beta 1-42)-alpha-fibrin, differences that disappeared when repolymerization of preformed fibrin monomers was carried out. Since existing data indicate that thrombin releases FPA in a concerted manner, resulting in relatively rapid evolution of fully functional divalent alpha-fibrin monomers, it can be inferred that delayed fibrin assembly of reptilase fibrin is due to slower formation of divalent alpha-fibrin monomers. Thrombin-activated des-(B beta 1-42)-alpha-fibrin polymerized more rapidly at low ionic strength (mu, 0.04) than did native alpha,beta-fibrin, a reversal of their behavior at physiological ionic strength (mu, 0.14). Concomitant measurement of FPA release revealed modest slowing of release at low ionic strength from des-(B beta 1-42)-fibrinogen (t1/2, 36.5 versus 21.5 min) and marked slowing from native fibrinogen (t1/2, 138 versus 22.2 min). This behavior correlated with increased thrombin binding to native alpha,beta-fibrin at low ionic strength, coupled with weak thrombin binding to des-(B beta 1-42)-alpha-fibrin, and indicates that secondary thrombin binding plays an important role in regulating thrombin diffusion and catalytic activity. Des-(B beta 1-42)-fibrinogen lacks or has a markedly defective secondary thrombin-binding site, from which we conclude that the B beta 15-42 sequence in fibrin plays a major role in forming or providing this site.

Batroxobin↗
PubMed1990

Structural model of factors V and Va based on scanning transmission electron microscope images and mass analysis.

Coagulation factor V (fV) is a single-chain glycoprotein (Mr 330,000; domain structure A1-A2-B-A3-C1-C2) that is activated to factor Va (fVa; Mr 174,000) by thrombin, which cleaves away the B domain leaving a heterodimeric structure composed of a heavy chain (A1-A2; Mr 94,000) and a light chain (A3-C1-C2; Mr 74,000). We analyzed the ultrastructure of scanning transmission electron microscope images of bovine and human fV, bovine fVa, and its constituent light chains and heavy chains. Factor V molecules had irregularly globular (10-12 nm) to oblong (8-14 nm) core structures which commonly displayed a peripheral satellite appendage of variable morphology attached to the core by a narrow stalk. Scanning transmission electron microscope mass analyses indicated that monomolecular bovine fV molecules had a mass of 322 +/- 45 kDa and human fV, 315 +/- 31 kDa. Factor Va molecules were irregular, globular (8-12 nm) structures that resembled the fV core structure, lacked the satellite appendage representing B domainal structures, and had a mass of 180 +/- 22 kDa. Our findings permit us to propose a structural model of fV suggesting the relative orientation of its closely associated light chain and heavy chain core components and indicating that these constituents remain associated in the transition from fV to fVa.

Animals↗
PubMed1990

Human plasma fibronectin structure probed by steady-state fluorescence polarization: evidence for a rigid oblate structure.

In order to more clearly define the structure of human plasma fibronectin (PFn) under physiologic buffer conditions, we determined the mean harmonic rotational relaxation times (rho H) of PFn and the thrombin-derived 190/170-kDa PFn fragment using steady-state fluorescence polarization. These measurements utilized the long lifetime emission (tau = 1.2 X 10(-7) S) exhibited by 1-pyrenebutyrate, which had been covalently attached to amino groups at random sites on the PFn subunit. Our data analysis assumed that two independent processes depolarize the fluorescence exhibited by the dansylcadaverine and 1-pyrenebutyrate conjugates of PFn: (A) rapid (rho H less than 10(-9) S) "thermally-activated" localized rotational motion of the protein side chains bearing the fluorescent probe [Weber, G. (1952) Biochem. J. 51, 145-154] and (B) slow (rho H approximately 10(-6) S) temperature-independent global rotational motion of the whole PFn molecule. Since only the rho H associated with the latter process is a true hydrodynamic parameter (i.e., sensitive to size and/or shape of the PFn molecule), we utilized isothermal polarization measurements to discriminate against the interfering signal arising from "thermally activated" probe rotation. The rho H (4.4 +/- 0.9 microseconds) derived from an experiment in which pyrene-PFn fluorescence polarization was monitored as a function of sucrose concentration at constant temperature is 7 (+/- 1.4) times longer than that predicted for an equivalent hydrated sphere. We propose that "thermally activated" probe rotation gives rise to the nearly 100-fold shorter PFn rho H values previously reported in the literature. Consequently, our data exclude all previous models which invoke segmental flexibility of the PFn peptide backbone. The simplest hydrodynamic model supported by our fluorescence data is an oblate ellipsoid with an axial ratio of 15:1. All prolate models can be unambiguously excluded by this result. We estimate that the disk-shaped PFn molecule has a diameter and thickness of 30 and 2 nm, respectively. Electron microscopy of negatively stained PFn specimens on carbon also showed PFn to have a compact rounded structure. The much faster rotational relaxation rate of the pyrene-190/170-kDa PFn fragment (rho H = 0.92 +/- 0.11 microseconds) compared to pyrene-PFn indicated that this monomeric PFn fragment, like native PFn, had an oblate shape under physiologic buffer conditions.

Chromatography, Affinity↗
PubMed1990

The acceleratory effect of thrombin on fibrin clot assembly.

Inhibition of thrombin proteolysis of fibrinogen with D-phenylalanyl-L-propyl-L-arginine chloromethyl ketone (PPACK) results in irreversible inactivation of the thrombin catalytic site, but the PPACK-inhibited thrombin, through its exosite, retains its ability to bind to fibrinogen or fibrin. Hirudin inactivates thrombin at the catalytic site and also inhibits thrombin exosite binding to fibrin or fibrinogen. PPACK or hirudin was added to a clotting mixture of fibrinogen and active thrombin (enzyme:substrate ratio, 1:400 and 1:800) prior to the onset of gelation. Subsequent fibrin assembly was evaluated by turbidity measurements at 350 nm and by determining the fibrin and fibrinogen content of the clots that ultimately formed. Polymerization rates and the fibrin/fibrinogen content of the clots that formed were greater in the PPACK-inhibited system than in the hirudin-inhibited system. Lowering the ionic strength from 0.14 to 0.09 amplified these differences. The results suggest that in addition to its well-recognized role in the proteolytic conversion of fibrinogen to fibrin, thrombin functions as a cofactor in the fibrin assembly process.

Amino Acid Chloromethyl Ketones↗
PubMed1990

Structural model of porcine factor VIII and factor VIIIa molecules based on scanning transmission electron microscope (STEM) images and STEM mass analysis.

Porcine plasma factor VIII (fVIII) molecules are heterodimers composed of a 76,000-mol wt light chain (-A3-C1-C2) and a heavy chain ranging in molecular weight from 82,000 (A1-A2) to 166,000 (A1-A2-B). Proteolytic activation of fVIII by thrombin results in fVIIIa heterotrimers lacking B domains (A1, A2, A3-C1-C2). In this study, immunoaffinity purified fVIII was further fractionated by mono S or mono Q chromatography to prepare heterodimers containing a light chain and an A1-A2-B heavy chain (fVIII 166/76) or an A1-A2 heavy chain (fVIII 82/76). Mass analysis of scanning transmission electron microscopic (STEM) images of fVIII 166/76 indicated that heterodimers (mass 237 +/- 20 kD) had irregularly globular core structures 10-12 nm across, and frequently displayed a diffuse, occasionally globular to ovoid satellite structure extending 5-14 nm from the core, and attached to it by a thin stalk. Factor VIII 82/76 molecules (mass 176 +/- 20 kD) had the same core structures as fVIII 166/76 molecules, but lacked the satellite structure. These findings indicate that A1-A2 domains of heavy chains and the light chains of the fVIII procofactor molecule are closely associated and constitute the globular core structure, whereas the B domainal portion of heavy chains comprises the peripheral satellite appendage. Factor VIII core structures commonly displayed a finger-like projection near the origin of the B domainal stalk that was also a consistent feature of the free heavy chains (mass 128-162 kD) found in fVIII 166/76 preparations. Factor VIII light chain monomers (mass, 76 +/- 16 kD) were globular to c-shaped particles 6-8 nm across. These chains commonly possessed a v-shaped projection originating from its middle region, that could also be observed at the periphery of fVIII core molecules. Factor VIIIa preparations contained heterotrimers (mass 162 +/- 13 kD) that had the same dimensions as fVIII core structures, lacked the B domainal appendage, and sometimes possessed the same core features as fVIII molecules. Molecular species corresponding to heterodimers (mass, 128 +/- 13 kD) and unassociated subunit chains (40-100 kD) were also observed in fVIIIa preparations, suggesting that heterotrimers have an appreciable tendency to dissociate, a phenomenon that could explain the decay of fVIIIa activity after thrombin activation of fVIII.

Animals↗
PubMed1990

Fibrin polymerization and its regulatory role in hemostasis.

Proteolytic conversion of fibrinogen to fibrin results in self-assembly to form a three-dimensional clot matrix that subsequently becomes cross-linked by fXIIIa to form the central structural element of the in vivo thrombus. The process of fibrin formation and assembly leads to new properties that serve to regulate the rate and extent of clotting, cross-linking, and fibrinolysis. These are brought about by the ability of fibrin (1) to bind thrombin at a noncatalytic site, thus limiting its diffusability but at the same time preserving its catalytic potential; (2) to bind fXIII, regulate its activation to fXIIIa, and limit further activation of fXIII once fibrin cross-linking has occurred; and (3) to bind alpha 2-PI, tPA, and plasminogen and regulate the initiation and propagation of fibrinolysis. Additional interactions not covered in this review between fibrin(ogen), and other plasma proteins, cells or matrix components suggest other functions for fibrin that, along with those discussed above, define a critical role in modulating hemostasis, inflammation, and the wound healing process.

Extracellular Matrix↗
PubMed1989

The polymerization of fibrin prepared from fibrinogen Haifa (gamma 275Arg----His).

Fibrinogen Haifa is a congenital heterozygous fibrinogen variant (gamma 275 Arg----His) characterized by prolonged thrombin and reptilase times and normal fibrinopeptide (FPA, FPB) release. We compared the polymerization rate (by turbidity measurements at 350 nm) and the ultrastructure of Haifa alpha-, beta-, and alpha, beta-fibrin with that of normal. Haifa alpha, beta-fibrin polymerized less rapidly than did normal and formed a highly branched matrix with a smaller mean fiber diameter; this network closely resembled that of normal alpha, beta-fibrin with EDTA added. In the presence of CaCl2 (1 to 10 mM), Haifa alpha, beta-fibrin polymerized more rapidly than in buffer alone and possessed a matrix structure closely resembling that of normal fibrin. From these observations it appears that the functional defect in Haifa fibrin can be related to the inability of the abnormal molecule to effectively utilize available calcium. The polymerization profile of Haifa alpha-fibrin differed only modestly from that of normal alpha-fibrin, whereas that of Haifa beta-fibrin was markedly impaired. This finding plus similarities in the ultrastructure of Haifa and normal alpha-fibrin specimens suggests that the defective gamma chain structure of Haifa fibrinogen results in greater impairment of the carboxy terminal "b" polymerization domain reacting with the site exposed by cleavage of FPB ("B" site) than it does that of the carboxy terminal "a" domain reacting with the site exposed by cleavage of FPA ("A" site). Whether this effect is due to absolute differences in the degree of impairment of these two types of polymerization sites, or whether proper utilization of the "B" to "b" site is dependent upon participation of the "A" to "a" site remains to be determined.

Calcium↗
PubMed1989

Identification of covalently linked trimeric and tetrameric D domains in crosslinked fibrin.

Following proteolytic conversion of fibrinogen to fibrin, clot assembly commences with formation of double-stranded fibrils that subsequently branch extensively in forming a three-dimensional network. Plasmin digests of fibrin clots that had first been covalently crosslinked by plasma transglutaminase (factor XIIIa) contained multimeric proteolytic fragments composed of crosslinked outer (D) domains of neighboring fibrin molecules. Two of these were larger than the well-known "D dimer" fragment and corresponded to D trimers and D tetramers, respectively. Whereas D dimers originate from crosslinked D domains at bimolecular junctions within two-stranded fibrils, D trimers and D tetramers evidently arise through crosslinking of contiguous D domains at trimolecular and tetramolecular junctions or at fibril branch points, respectively. Measurement of the widths of fibrils comprising trifunctional branches in thin fiber networks revealed tetramolecular branch points, which are formed by bifurcation of two double-stranded fibrils. In addition, another type of trifunctional structure, which we term the trimolecular branch point, was composed of three double-stranded fibrils. Crosslinking of D domains to form trimers may occur at this type of junction. These findings add to our understanding of the crosslinking arrangements that stabilize fibrin clot structure and the ways that fibrin molecules polymerize to form branches in the clot matrix.

Cross-Linking Reagents↗
PubMed1989

Fatal small-bowel necrosis and pulmonary hypertension in sickle cell disease.

Initial enthusiasm for the use of vasodilators to improve pulmonary hemodynamics and symptomatic status in pulmonary hypertension of diverse etiologies has been tempered by the high incidence of serious complications, especially hypotension. However, the unrelenting hypoxia of pulmonary hypertension without treatment and the improved pulmonary hemodynamics and symptomatic states of some patients during vasodilator therapy provide the rationale for a therapeutic test of vasodilators in hemodynamically monitored patients. We report that vasodilator therapy in a patient with severe hypoxia due to pulmonary hypertension and sickle cell crisis was fatally complicated by hypotension and extensive small-bowel infarction.

Adult↗
PubMed1988

Evidence that binding to the carboxyl-terminal heparin-binding domain (Hep II) dominates the interaction between plasma fibronectin and heparin.

We assessed the participation of the three known heparin-binding domains of PFn (Hep I, Hep II, Hep III) in their interaction with heparin by making a quantitative comparison of the fluid-phase heparin affinities of PFn and PFn fragments under physiologic pH and ionic strength conditions. Using a fluorescence polarization binding assay that employed a PFn affinity-purified fluorescein-labeled heparin preparation, we found that greater than 98% of the total PFn heparin-binding sites exhibit a Kd in the 118-217 nM range. We also identified a minor (less than 2%) class of binding sites exhibiting very high affinity (Kd approximately 1 nM) in PFn and the carboxyl-terminal 190/170 and 150/136 kDa PFn fragments. This latter activity probably reflects multivalent inter- or intramolecular heparin-binding activity. Amino-terminal PFn fragments containing Hep I (72 and 29 kDa) exhibited low affinity for heparin under physiologic buffer conditions (Kd approximately 30,000 mM). PFn fragments (190/170 and 150/136 kDa) containing both the carboxyl-terminal Hep II and central Hep III domains retained most of the heparin-binding activity of native PFn (Kd = 278-492 nM). The isolated Hep II domain (33-kDa fragment) exhibited appreciable, but somewhat lower (2-5-fold), heparin affinity compared to the 190/170-kDa PFn fragment. Heparin binding to the 100-kDa PFn fragment containing Hep III was barely detectable (Kd greater than 30,000 nM). From these observations, we conclude that PFn contains only one major functional heparin-binding site per subunit, Hep II, that dominates the interaction between heparin and PFn.

Binding Sites↗
PubMed1988

The role of fibrinogen A alpha chains in ADP-induced platelet aggregation in the presence of fibrinogen molecules containing gamma' chains.

Human plasma fibrinogen (Fgn) is heterogenous with respect to the size of its gamma chains, which differ in that residues 408 to 411 of gammaA chains (93% of total) are replaced in gamma' chains by a unique 20 amino acid sequence (gamma408 to gamma427). In this study, we compared the contribution to adenosine diphosphate (ADP)-induced platelet aggregation of the A alpha chains in Fgn molecules containing predominantly (fraction 1-2) or exclusively (peak 1 Fgn) gammaA chains with that of molecules containing approximately 50% gamma' chains (peak 2 Fgn). Using washed human platelets, we confirmed that the number of peak 2 Fgn molecules binding to platelets in the presence of ADP was about half the number of peak 1 Fgn molecules (18,962 +/- 2,298 v 44,366 +/- 16,096 molecules per platelet), and that isolated S-carboxymethylated (SCM) gammaA chains supported ADP-induced platelet aggregation nearly as well as peak 1 Fgn. In contrast, SCM-gamma' chains alone supported aggregation poorly, whereas a mixture of SCM-gammaA and gamma' chains (1:1 ratio) gave intermediate results. Despite the findings with isolated SCM-gamma' chains, we found that peak 2 Fgn supported platelet aggregation nearly as well as peak 1 Fgn. However, peak 2 Fgn from which carboxy (COOH)-terminal A alpha chain segments had been removed by digestion with plasmin showed a markedly decreased platelet aggregation potential. Peak 1 Fgn core fraction from an 88% to 90% coagulable plasmin digest, or Fgn fraction 1-9, which has a high gammaA/gamma' chain ratio (93:7), but lacks COOH-terminal regions of A alpha chains, supported platelet aggregation to the same extent as did intact peak 2 Fgn. These findings indicate that Fgn molecules containing gamma' chains can approach the aggregation potential of Fgn molecules containing predominantly or exclusively gammaA chains only if intact A alpha chains are also present.

Adenosine Diphosphate↗
PubMed1988

Fibrinogen Birmingham: a heterozygous dysfibrinogenemia (A alpha 16 Arg----His) containing heterodimeric molecules.

Fibrinogen was isolated from the plasma of a 25-year-old female with a history of mild bleeding and several recent moderate to severe hemorrhagic episodes. Coagulability with thrombin approached 100% and varied directly with the time of incubation with the enzyme. High-performance liquid chromatography analysis of thrombin-induced fibrinopeptide release demonstrated retarded fibrinopeptide A (FPA) and fibrinopeptide B (FPB) release and the presence of an abnormal A peptide (FPA) amounting to 50% of the total. The same biochemical abnormalities were found in her asymptomatic father. Amino acid analysis and carboxypeptidase digestion of FPA demonstrated the substitution of His for Arg at A alpha 16. In contrast to the thrombin- and reptilase-sensitive Arg-Gly bond in the normal A alpha chain, the abnormal A alpha chain (A alpha) sequence is resistant to reptilase attack but is slowly cleaved by thrombin. To evaluate whether Birmingham A alpha and A alpha chains had been assembled nonselectively into heterodimeric (ie, 50% A alpha, A alpha) and homodimeric (ie, 25% A alpha, A alpha; 25% A alpha, A alpha) species, the clot and the clot liquor resulting from reptilase treatment of normal or Birmingham fibrinogen were separated, and each was then further incubated with thrombin to release remaining fibrinopeptides. Assuming that fibrinogen Birmingham contained heterodimeric molecules and that these and the normal molecules were completely incorporated into a reptilase clot, the expected coagulability would be 75%. In addition, subsequent thrombin treatment of the reptilase clot would release 50% of the total FPA and 75% of the total FPB present in the original sample. On the other hand, if only homodimeric fibrinogen species (50% A alpha, A alpha; 50% A alpha, A alpha) existed, the maximum reptilase coagulability would be 50%, and after thrombin treatment, 50% of the total FPB and no FPA would be recovered from the reptilase clot. We found the propositus's fibrinogen to be 68% coagulable, and we recovered 45% of the FPA and 70% of the FPB from the reptilase clot. Essentially the same coagulability and distribution of fibrinopeptides was found in the reptilase clot from her father's fibrinogen. We therefore conclude that fibrinogen Birmingham contains heterodimeric species (A alpha, A alpha) amounting to approximately 50% of the circulating fibrinogen molecules. The existence of heterodimers is consistent with a nonselective intracellular process of constituent chain assembly of dimeric plasma fibrinogen molecules.

Adult↗
PubMed1988

Essential thrombocythemia in pregnancy.

A 32-year-old women with essential thrombocythemia and a history of bleeding completed a full-term pregnancy. During pregnancy, the platelet count declined markedly to near-normal levels, but returned to prepregnancy levels within two weeks after delivery. The clinical course was uneventful, except for two brief episodes of vaginal bleeding during the second trimester. Possible etiologic mechanisms for pregnancy-related reduction of platelet levels in thrombocythemia include increased platelet consumption or down-regulation of platelet production by a placental or fetal factor.

Adult↗
PubMed1987

Studies on the ultrastructure of fibrin lacking fibrinopeptide B (beta-fibrin).

Release of fibrinopeptide B from fibrinogen by copperhead venom procoagulant enzyme results in a form of fibrin (beta-fibrin) with weaker self-aggregation characteristics than the normal product (alpha beta-fibrin) produced by release of fibrinopeptides A (FPA) and B (FPB) by thrombin. We investigated the ultrastructure of these two types of fibrin as well as that of beta-fibrin prepared from fibrinogen Metz (A alpha 16 Arg----Cys), a homozygous dysfibrinogenemic mutant that does not release FPA. At 14 degrees C and physiologic solvent conditions (0.15 mol/L of NaCl, 0.015 mol/L of Tris buffer pH 7.4), the turbidity (350 nm) of rapidly polymerizing alpha beta-fibrin (thrombin 1 to 2 U/mL) plateaued in less than 6 min and formed a "coarse" matrix consisting of anastomosing fiber bundles (mean diameter 92 nm). More slowly polymerizing alpha beta-fibrin (thrombin 0.01 and 0.001 U/mL) surpassed this turbidity after greater than or equal to 60 minutes and concomitantly developed a network of thicker fiber bundles (mean diameters 118 and 186 nm, respectively). Such matrices also contained networks of highly branched, twisting, "fine" fibrils (fiber diameters 7 to 30 nm) that are usually characteristic of matrices formed at high ionic strength and pH. Slowly polymerizing beta-fibrin, like slowly polymerizing alpha beta-fibrin, displayed considerable quantities of fine matrix in addition to an underlying thick cable network (mean fiber diameter 135 nm), whereas rapidly polymerizing beta-fibrin monomer was comprised almost exclusively of wide, poorly anastomosed, striated cables (mean diameter 212 nm). Metz beta-fibrin clots were more fragile than those of normal beta-fibrin and were comprised almost entirely of a fine network. Metz fibrin could be induced, however, to form thick fiber bundles (mean diameter 76 nm) in the presence of albumin at a concentration (500 mumol/L) in the physiologic range and resembled a Metz plasma fibrin clot in that regard. The diminished capacity of Metz beta-fibrin to form thick fiber bundles may be due to impaired use or occupancy of a polymerization site exposed by FPB release. Our results indicate that twisting fibrils are an inherent structural feature of all forms of assembling fibrin, and suggest that mature beta-fibrin or alpha beta-fibrin clots develop from networks of thin fibrils that have the ability to coalesce to form thicker fiber bundles.

Blood Coagulation↗