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Propagation of blood clotting in the complex biochemical network of hemostasis is described by a simple mechanism

Runyon, Matthew K. and Johnson-Kerner, Bethany L. and Kastrup, Christian J. and Van Ha, Thuong G. and Ismagilov, Rustem F. (2007) Propagation of blood clotting in the complex biochemical network of hemostasis is described by a simple mechanism. Journal of the American Chemical Society, 129 (22). pp. 7014-7015. ISSN 0002-7863. https://resolver.caltech.edu/CaltechAUTHORS:20130821-160729975

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Abstract

Hemostasis is the complex biochemical network that controls blood clotting. We previously described a chemical model that mimicked the dynamics of hemostasis based on a simple regulatory mechanisma threshold response due to the competition between production and removal of activators. Here, we used human blood plasma in phospholipid-coated microfluidic channels to test predictions based on this mechanism. We demonstrated that, for a given geometry of channels, clot propagation from an obstructed channel into a channel with flowing blood plasma is dependent on the shear rate in the channel with flowing blood plasma. If confirmed in vivo, these results may explain clot propagation from a small vessel to a larger, clinically relevant vessel. In addition, these results would further validate the use of modular mechanisms, simplified chemical models, and microfluidics to study complex biochemical networks.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja072602pDOIArticle
http://pubs.acs.org/doi/full/10.1021/ja072602pPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ja072602pPublisherSupporting Information
ORCID:
AuthorORCID
Ismagilov, Rustem F.0000-0002-3680-4399
Additional Information:Copyright © 2007 American Chemical Society. Published In Issue: June 06, 2007. Received April 13, 2007. This work was funded by the ONR (Grant N000140610630), the Camille Dreyfus Teacher-Scholar Awards Program, and the NSF CAREER Award (CHE-0349034). M.K.R. was supported in part by Burroughs Wellcome Fund Interfaces I.D. 1001774. R.F.I. is a Cottrell Scholar of Research Corporation and an A. P. Sloan Research Fellow. Some of this work was performed at the MRSEC microfluidic facility (funded by the NSF). We thank Jessica M. Price for contributions in editing and writing this manuscript. Supporting Information Available Detailed procedure for experiments and movie comparing the recirculation in the “valve” at high and low shear rates. This material is available free of charge via the Internet at http://pubs.acs.org.
Funders:
Funding AgencyGrant Number
ONRN000140610630
Camille and Henry Dreyfus FoundationUNSPECIFIED
NSFCHE-0349034
Burroughs Wellcome Fund Interfaces1001774
Cottrell Scholar of Research CorporationUNSPECIFIED
Alfred P. Sloan FoundationUNSPECIFIED
Subject Keywords:tissue factor; thrombus formation; coagulation; model; flow
Issue or Number:22
Record Number:CaltechAUTHORS:20130821-160729975
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20130821-160729975
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:40860
Collection:CaltechAUTHORS
Deposited By: Whitney Barlow
Deposited On:27 Aug 2013 22:37
Last Modified:03 Oct 2019 05:43

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