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Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the complex network of hemostasis

Kastrup, Christian J. and Runyon, Matthew K. and Shen, Feng and Ismagilov, Rustem F. (2006) Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the complex network of hemostasis. Proceedings of the National Academy of Sciences of the United States of America, 103 (43). pp. 15747-15752. ISSN 0027-8424. PMCID PMC1635074.

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This article demonstrates that a simple chemical model system, built by using a modular approach, may be used to predict the spatiotemporal dynamics of initiation of blood clotting in the complex network of hemostasis. Microfluidics was used to create in vitro environments that expose both the complex network and the model system to surfaces patterned with patches presenting clotting stimuli. Both systems displayed a threshold response, with clotting initiating only on isolated patches larger than a threshold size. The magnitude of the threshold patch size for both systems was described by the Damkohler number, measuring competition of reaction and diffusion. Reaction produces activators at the patch, and diffusion removes activators from the patch. The chemical model made additional predictions that were validated experimentally with human blood plasma. These experiments show that blood can be exposed to significant amounts of clot-inducing stimuli, such as tissue factor, without initiating clotting. Overall, these results demonstrate that such chemical model systems, implemented with microfluidics, may be used to predict spatiotemporal dynamics of complex biochemical networks.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle Information
Shen, Feng0000-0002-4709-330X
Ismagilov, Rustem F.0000-0002-3680-4399
Additional Information:© 2006 by The National Academy of Sciences of the USA. Edited by George M. Whitesides, Harvard University, Cambridge, MA, and approved August 30, 2006 (received for review July 3, 2006). We thank Shaun R. Coughlin, Jay T. Groves, Satish Kumar, Yannis Kevrekidis, Daniel Koshland, Ka Yee Lee, Jonathan L. Miller, Atul Parikh, Thuong Van Ha, and Ding-Djung Yang for discussions and advice. This work was supported in part by National Science Foundation CAREER Award CHE-0349034 and Office of Naval Research Grant N00014-03-10482. M.K.R. was supported by Burroughs Wellcome Fund Interfaces ID 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 Materials Research Science and Engineering Centers microfluidic facility (funded by the National Science Foundation). Author contributions: C.J.K., M.K.R., and R.F.I. designed research; C.J.K., M.K.R., and F.S. performed research; C.J.K. and M.K.R. contributed new reagents/analytic tools; C.J.K., M.K.R., F.S., and R.F.I. analyzed data; and C.J.K., M.K.R., and R.F.I. wrote the paper. The authors declare no conflict of interest. This article is a PNAS direct submission.
Funding AgencyGrant Number
Office of Naval Research (ONR)N00014-03-10482
Burroughs Wellcome Fund1001774
Cottrell Scholar of Research CorporationUNSPECIFIED
Alfred P. Sloan FoundationUNSPECIFIED
Issue or Number:43
PubMed Central ID:PMC1635074
Record Number:CaltechAUTHORS:20130821-160721372
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:40808
Deposited By: Whitney Barlow
Deposited On:27 Aug 2013 23:33
Last Modified:03 Jun 2020 19:38

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