dc.contributor.author | Melvin, Adam T. | |
dc.contributor.author | Welf, Erik S. | |
dc.contributor.author | Wang, Yana | |
dc.contributor.author | Irvine, Darrell J. | |
dc.contributor.author | Haugh, Jason M. | |
dc.date.accessioned | 2014-12-16T14:00:50Z | |
dc.date.available | 2014-12-16T14:00:50Z | |
dc.date.issued | 2011-04 | |
dc.date.submitted | 2010-08 | |
dc.identifier.issn | 00063495 | |
dc.identifier.issn | 1542-0086 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/92313 | |
dc.description.abstract | 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. | en_US |
dc.description.sponsorship | National Science Foundation (U.S.) (0828936) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (GM074711) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (EB007280) | en_US |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/j.bpj.2011.02.047 | en_US |
dc.rights | Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. | en_US |
dc.source | Elsevier | en_US |
dc.title | In Chemotaxing Fibroblasts, Both High-Fidelity and Weakly Biased Cell Movements Track the Localization of PI3K Signaling | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Melvin, Adam T., Erik S. Welf, Yana Wang, Darrell J. Irvine, and Jason M. Haugh. “In Chemotaxing Fibroblasts, Both High-Fidelity and Weakly Biased Cell Movements Track the Localization of PI3K Signaling.” Biophysical Journal 100, no. 8 (April 2011): 1893–1901. © 2011 Biophysical Society. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biological Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemical Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Materials Science and Engineering | en_US |
dc.contributor.mitauthor | Wang, Yana | en_US |
dc.contributor.mitauthor | Irvine, Darrell J. | en_US |
dc.relation.journal | Biophysical Journal | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Melvin, Adam T.; Welf, Erik S.; Wang, Yana; Irvine, Darrell J.; Haugh, Jason M. | en_US |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |