Fibrin Networks Regulate Protein Transport during Thrombus Development

Kim, Oleg V.; Xu, Zhiliang; Rosen, Elliot D.; Alber, Mark S.

doi:10.1371/journal.pcbi.1003095

Fibrin Networks Regulate Protein Transport during Thrombus Development

Journal Article · Thu Jun 13 00:00:00 EDT 2013 · PLoS Computational Biology (Online)

DOI:https://doi.org/10.1371/journal.pcbi.1003095· OSTI ID:2469535

Kim, Oleg V. ^[1]; Xu, Zhiliang ^[1]; Rosen, Elliot D. ^[2]; Alber, Mark S. ^[3]

University of Notre Dame, South Bend, IN (United States)
Indiana University School of Medicine, Indianapolis, IN (United States)
University of Notre Dame, South Bend, IN (United States); Indiana University School of Medicine, Indianapolis, IN (United States)

Thromboembolic disease is a leading cause of morbidity and mortality worldwide. In the last several years there have been a number of studies attempting to identify mechanisms that stop thrombus growth. This paper identifies a novel mechanism related to formation of a fibrin cap. In particular, protein transport through a fibrin network, an important component of a thrombus, was studied by integrating experiments with model simulations. The network permeability and the protein diffusivity were shown to be important factors determining the transport of proteins through the fibrin network. Our previous in vivo studies in mice have shown that stabilized non-occluding thrombi are covered by a fibrin network (‘fibrin cap’). Model simulations, calibrated using experiments in microfluidic devices and accounting for the permeable structure of the fibrin cap, demonstrated that thrombin generated inside the thrombus was washed downstream through the fibrin network, thus limiting exposure of platelets on the thrombus surface to thrombin. Moreover, by restricting the approach of resting platelets in the flowing blood to the thrombus core, the fibrin cap impaired platelets from reaching regions of high thrombin concentration necessary for platelet activation and limited thrombus growth. The formation of a fibrin cap prevents small thrombi that frequently develop in the absence of major injury in the 60000 km of vessels in the body from developing into life threatening events.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Science Foundation (NSF); USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2469535

Journal Information:: PLoS Computational Biology (Online), Journal Name: PLoS Computational Biology (Online) Journal Issue: 6 Vol. 9; ISSN 1553-7358

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
Biochemistry & Molecular Biology
Fibrin
Fibrinogen
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Hemodynamics
Mathematical & Computational Biology
Permeability
Platelet activation
Platelets
Thrombin

Fibrin Networks Regulate Protein Transport during Thrombus Development

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