title: The molecular weights, mass distribution, chain composition, and structure of soluble fibrin degradation products released from a fibrin clot perfused with plasmin.
abstract: We used a perfused clot system to study the degradation of cross-linked fibrin. Multiangle laser light scattering showed that plasmin-mediated cleavage caused the release of noncovalently associated fibrin degradation products (FDPs) with a weight-averaged molar mass (Mw) of approximately 6 x 10(6) g/mol. The Mw of FDPs is dependent on ionic strength, and the Mw observed at 0.15 M NaCl resulted from the self-association of FDPs having Mw of approximately 3.8 x 10(6) g/mol. Complete solubilization required the cleavage of approximately 25% of fragment D/fragment E connections, with 48% alpha-, 62% beta-, and 42% gamma-chains cleaved. These results showed that D-E cleavage cannot be explained by a random mechanism, implying cooperativity. Gel filtration and multiangle laser light scattering showed that FDPs range from 2.5 x 10(5) to 1 x 10(7) g/mol. In addition to fragment E, FDPs are composed of fragments ranging from 2 x 10(5) Da (D-dimer, or DD) to at least 2.3 x 10(6) Da (DX8D). FDP mass distribution is consistent with a model whereby FDPs bind to fibrin with affinities proportional to fragment mass. Root mean square radius analysis showed that small FDPs approximate rigid rods, but this relationship breaks down as FDPs size increases, suggesting that large FDPs possess significant flexibility.
authors.affiliation: Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: J B
authors.initials: JB
authors.lastname: Walker
authors.forename: M E
authors.initials: ME
authors.lastname: Nesheim
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel; D005337:Fibrin / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D008027:Light; D008970:Molecular Weight; D011487:Protein Conformation; D018000:Receptors, Peptide / Q000737:chemistry* / Q000378:metabolism; D012542:Scattering, Radiation; D012965:Sodium Chloride