Physical Determinants of Fibrinolysis in Single Fibrin Fibers

DSpace/Manakin Repository

Physical Determinants of Fibrinolysis in Single Fibrin Fibers

Citable link to this page

 

 
Title: Physical Determinants of Fibrinolysis in Single Fibrin Fibers
Author: Bucay, Igal; O’Brien, E. Tim; Wulfe, Steven D.; Superfine, Richard; Wolberg, Alisa S.; Falvo, Michael R.; Hudson, Nathan E.

Note: Order does not necessarily reflect citation order of authors.

Citation: Bucay, 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.
Full Text & Related Files:
Abstract: Fibrin 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.
Published Version: doi:10.1371/journal.pone.0116350
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340865/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:14351216
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters