Structural origins of fibrin clot rheology.
The origins of clot rheological behavior associated with network morphology and factor XIIIa-induced cross-linking were studied in fibrin clots. Network morphology was manipulated by varying the concentrations of fibrinogen, thrombin, and calcium ion, and cross-linking was controlled by a synthetic, active-center inhibitor of FXIIIa. Quantitative measurements of network features (fiber lengths, fiber diameters, and fiber and branching densities) were made by analyzing computerized three-dimensional models constructed from stereo pairs of scanning electron micrographs. Large fiber diameters and lengths were established only when branching was minimal, and increases in fiber length were generally associated with increases in fiber diameter. Junctions at which three fibers joined were the dominant branchpoint type. Viscoelastic properties of the clots were measured with a rheometer and were correlated with structural features of the networks. At constant fibrinogen but varying thrombin and calcium concentrations, maximal rigidities were established in samples (both cross-linked and noncross-linked) which displayed a balance between large fiber sizes and great branching. Clot rigidity was also enhanced by increasing fiber and branchpoint densities at greater fibrinogen concentrations. Network morphology is only minimally altered by the FXIIIa-catalyzed cross-linking reaction, which seems to augment clot rigidity most likely by the stiffening of existing fibers.
Ryan
E A
EA
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Mockros
L F
LF
Weisel
J W
JW
Lorand
L
L
D001777:Blood Coagulation / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D026122:Factor XIIIa / Q000037:antagonists & inhibitors; D005337:Fibrin / Q000737:chemistry* / Q000378:metabolism*; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional; D007093:Imidazoles / Q000494:pharmacology; D012212:Rheology / Q000187:drug effects; D013917:Thrombin / Q000737:chemistry / Q000378:metabolism
D007093:Imidazoles; C088946:1,3,4,5-tetramethyl-2-((2-oxopropyl)thio)imidazolium; D005337:Fibrin; D005340:Fibrinogen; D026122:Factor XIIIa; D013917:Thrombin; D002118:Calcium