In Chemotaxing Fibroblasts, Both High-Fidelity and Weakly Biased Cell Movements Track the Localization of PI3K Signaling
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Melvin-2011-In Chemotaxing Fibro.pdf
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Author(s)
Melvin, Adam T.
Welf, Erik S.
Wang, Yana
Irvine, Darrell J.
Haugh, Jason M.
Date Issued
April 2011
Journal
Biophysical Journal
Publisher
Elsevier
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.
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Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
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DOI of Published Version
https://doi.org/10.1016/j.bpj.2011.02.047
