| In chemotaxing fibroblasts, both high-fidelity and weakly biased cell movements track the localization of PI3K signaling. | |
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MedLine Citation:
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PMID: 21504725 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cell movement biased by a chemical gradient, or chemotaxis, coordinates the recruitment of cells and collective migration of cell populations. During wound healing, chemotaxis of fibroblasts is stimulated by platelet-derived growth factor (PDGF) and certain other chemoattractants. Whereas the immediate PDGF gradient sensing response has been characterized previously at the level of phosphoinositide 3-kinase (PI3K) signaling, the sensitivity of the response at the level of cell migration bias has not yet been studied quantitatively. In this work, we used live-cell total internal reflection fluorescence microscopy to monitor PI3K signaling dynamics and cell movements for extended periods. We show that persistent and properly aligned (i.e., high-fidelity) fibroblast migration does indeed correlate with polarized PI3K signaling; accordingly, this behavior is seen only under conditions of high gradient steepness (>10% across a typical cell length of 50 μm) and a certain range of PDGF concentrations. Under suboptimal conditions, cells execute a random or biased random walk, but nonetheless move in a predictable fashion according to the changing pattern of PI3K signaling. Inhibition of PI3K during chemotaxis is accompanied by loss of both cell-substratum contact and morphological polarity, but after a recovery period, PI3K-inhibited fibroblasts often regain the ability to orient toward the PDGF gradient. |
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Authors:
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Adam T Melvin; Erik S Welf; Yana Wang; Darrell J Irvine; Jason M Haugh |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Biophysical journal Volume: 100 ISSN: 1542-0086 ISO Abbreviation: Biophys. J. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-20 Completed Date: 2011-08-11 Revised Date: 2012-05-04 |
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: 1893-901 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alginates
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chemistry Animals Cell Surface Extensions / drug effects, metabolism Chemotaxis* / drug effects Dose-Response Relationship, Drug Fibroblasts / cytology*, drug effects, enzymology* Glucuronic Acid / chemistry Hexuronic Acids / chemistry Mice Microspheres NIH 3T3 Cells Phosphatidylinositol 3-Kinases / metabolism* Platelet-Derived Growth Factor / chemistry, pharmacology Receptors, Platelet-Derived Growth Factor / metabolism Signal Transduction* / drug effects Stochastic Processes |
| Grant Support | |
ID/Acronym/Agency:
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EB007280/EB/NIBIB NIH HHS; GM074711/GM/NIGMS NIH HHS; R21 GM074711/GM/NIGMS NIH HHS; R21 GM074711-02/GM/NIGMS NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Alginates; 0/Hexuronic Acids; 0/Platelet-Derived Growth Factor; 576-37-4/Glucuronic Acid; 9005-32-7/alginic acid; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Receptors, Platelet-Derived Growth Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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