Physical Determinants of Fibrinolysis in Single Fibrin Fibers
O’Brien, E. Tim
Wulfe, Steven D.
Wolberg, Alisa S.
Falvo, Michael R.
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CitationBucay, Igal, E. Tim O’Brien, Steven D. Wulfe, Richard Superfine, Alisa S. Wolberg, Michael R. Falvo, and Nathan E. Hudson. 2015. “Physical Determinants of Fibrinolysis in Single Fibrin Fibers.” PLoS ONE 10 (2): e0116350. doi:10.1371/journal.pone.0116350. http://dx.doi.org/10.1371/journal.pone.0116350.
AbstractFibrin fibers form the structural backbone of blood clots; fibrinolysis is the process in which plasmin digests fibrin fibers, effectively regulating the size and duration of a clot. To understand blood clot dissolution, the influence of clot structure and fiber properties must be separated from the effects of enzyme kinetics and perfusion rates into clots. Using an inverted optical microscope and fluorescently-labeled fibers suspended between micropatterned ridges, we have directly measured the lysis of individual fibrin fibers. We found that during lysis 64 ± 6% of fibers were transected at one point, but 29 ± 3% of fibers increase in length rather than dissolving or being transected. Thrombin and plasmin dose-response experiments showed that the elongation behavior was independent of plasmin concentration, but was instead dependent on the concentration of thrombin used during fiber polymerization, which correlated inversely with fiber diameter. Thinner fibers were more likely to lyse, while fibers greater than 200 ± 30 nm in diameter were more likely to elongate. Because lysis rates were greatly reduced in elongated fibers, we hypothesize that plasmin activity depends on fiber strain. Using polymer physics- and continuum mechanics-based mathematical models, we show that fibers polymerize in a strained state and that thicker fibers lose their prestrain more rapidly than thinner fibers during lysis, which may explain why thick fibers elongate and thin fibers lyse. These results highlight how subtle differences in the diameter and prestrain of fibers could lead to dramatically different lytic susceptibilities.
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