Fibrin Networks Regulate Protein Transport during Thrombus Development

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere1003095
JournalPLoS Computational Biology
Volume9
Issue number6
DOIs
StatePublished - Jun 2013

Fingerprint

protein transport
fibrin
Protein Transport
Platelets
Fibrin
Thrombosis
Proteins
Protein
protein
thrombin
morbidity
Simulation Model
Thrombin
diffusivity
simulation
vessel
Blood Platelets
experiment
blood
Microfluidics

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Ecology
  • Molecular Biology
  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Computational Theory and Mathematics

Cite this

Fibrin Networks Regulate Protein Transport during Thrombus Development. / Kim, Oleg V.; Xu, Zhiliang; Rosen, Elliot; Alber, Mark S.

In: PLoS Computational Biology, Vol. 9, No. 6, e1003095, 06.2013.

Research output: Contribution to journalArticle

Kim, Oleg V. ; Xu, Zhiliang ; Rosen, Elliot ; Alber, Mark S. / Fibrin Networks Regulate Protein Transport during Thrombus Development. In: PLoS Computational Biology. 2013 ; Vol. 9, No. 6.
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