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Biophys J. 2011 Apr 20;100(8):1893-901. doi: 10.1016/j.bpj.2011.02.047.

In chemotaxing fibroblasts, both high-fidelity and weakly biased cell movements track the localization of PI3K signaling.

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1
Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, USA.

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.

PMID:
21504725
PMCID:
PMC3077704
DOI:
10.1016/j.bpj.2011.02.047
[Indexed for MEDLINE]
Free PMC Article
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