| Confinement regulates complex biochemical networks: initiation of blood clotting by "diffusion acting". | |
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MedLine Citation:
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PMID: 19843446 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study shows that environmental confinement strongly affects the activation of nonlinear reaction networks, such as blood coagulation (clotting), by small quantities of activators. Blood coagulation is sensitive to the local concentration of soluble activators, initiating only when the activators surpass a threshold concentration, and therefore is regulated by mass transport phenomena such as flow and diffusion. Here, diffusion was limited by decreasing the size of microfluidic chambers, and it was found that microparticles carrying either the classical stimulus, tissue factor, or a bacterial stimulus, Bacillus cereus, initiated coagulation of human platelet-poor plasma only when confined. A simple analytical argument and numerical model were used to describe the mechanism for this phenomenon: confinement causes diffusible activators to accumulate locally and surpass the threshold concentration. To interpret the results, a dimensionless confinement number, Cn, was used to describe whether a stimulus was confined, and a Damköhler number, Da(2), was used to describe whether a subthreshold stimulus could initiate coagulation. In the context of initiation of coagulation by bacteria, this mechanism can be thought of as "diffusion acting", which is distinct from "diffusion sensing". The ability of confinement and diffusion acting to change the outcome of coagulation suggests that confinement should also regulate other biological "on" and "off" processes that are controlled by thresholds. |
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Authors:
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Feng Shen; Rebecca R Pompano; Christian J Kastrup; Rustem F Ismagilov |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Biophysical journal Volume: 97 ISSN: 1542-0086 ISO Abbreviation: Biophys. J. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-21 Completed Date: 2010-02-12 Revised Date: 2010-10-22 |
Medline Journal Info:
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Nlm Unique ID: 0370626 Medline TA: Biophys J Country: United States |
Other Details:
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Languages: eng Pagination: 2137-45 Citation Subset: IM |
Affiliation:
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Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Algorithms Bacillus cereus Blood Coagulation / physiology* Computer Simulation Diffusion* Environment Enzyme Precursors / metabolism Fluorescence Humans Kinetics Linear Models Microfluidic Analytical Techniques Models, Biological* Nonlinear Dynamics Plasma / physiology Thrombin / metabolism Thromboplastin / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Precursors; 9035-58-9/Thromboplastin; EC 3.4.21.-/meizothrombin; EC 3.4.21.5/Thrombin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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