Dataset Information

Physical determinants of fibrinolysis in single fibrin fibers.

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.

SUBMITTER: Bucay I

PROVIDER: S-EPMC4340865 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Physical determinants of fibrinolysis in single fibrin fibers.

Bucay Igal I O'Brien E Tim ET Wulfe Steven D SD Superfine Richard R Wolberg Alisa S AS Falvo Michael R MR Hudson Nathan E NE

PloS one 20150225 2

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 ...[more]

PMID: 25714359

Similar Datasets

Project description:Proper wound healing necessitates both coagulation (the formation of a blood clot) and fibrinolysis (the dissolution of a blood clot). A thrombus resistant to clot dissolution can obstruct blood flow, leading to vascular pathologies. This study seeks to understand the mechanisms by which individual fibrin fibers, the main structural component of blood clots, are cleared from a local volume during fibrinolysis. We observed 2-D fibrin networks during lysis by plasmin, recording the clearance of each individual fiber. We found that, in addition to transverse cleavage of fibers, there were multiple other pathways by which clot dissolution occurred, including fiber bundling, buckling, and collapsing. These processes are all influenced by the concentration of plasmin utilized in lysis. The network fiber density influenced the kinetics and distribution of these pathways. Individual cleavage events often resulted in large morphological changes in network structure, suggesting that the inherent tension in fibers played a role in fiber clearance. Using images before and after a cleavage event to measure fiber lengths, we estimated that fibers are strained ~23% beyond their equilibrium length during polymerization. To understand the role of fiber tension in fibrinolysis we modeled network clearance under differing amounts of fiber polymerized strain (prestrain). The comparison of experimental and model data indicated that fibrin tension enables 35% more network clearance due to network rearrangements after individual cleavage events than would occur if fibers polymerized in a non-tensed state. Our results highlight many characteristics and mechanisms of fibrin breakdown, which have implications on future fibrin studies, our understanding of the fibrinolytic process, and the development of thrombolytic therapies. STATEMENT OF SIGNIFICANCE: Fibrin fibers serve as the main structural element of blood clots. They polymerize under tension and have remarkable extensibility and elasticity. After the cessation of wound healing, fibrin must be cleared from the vasculature by the enzyme plasmin in order to resume normal blood flow: a process called fibrinolysis. In this study we investigate the mechanisms that regulate the clearance of individual fibrin fibers during fibrinolysis. We show that the inherent tension in fibers enhances the action of plasmin because every fiber cleavage event results in a redistribution of the network tension. This network re-equilibration causes fibers to buckle, bundle, and even collapse, leading to a more rapid fiber clearance than plasmin alone could provide.

Dataset Information

Physical determinants of fibrinolysis in single fibrin fibers.

Publications

Physical determinants of fibrinolysis in single fibrin fibers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets