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Published online 28 November 2005. doi:10.1083/jcb.200509028
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 171, Number 5, 883-892
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Article

Quantitative elucidation of a distinct spatial gradient-sensing mechanism in fibroblasts



Ian C. Schneider and Jason M. Haugh

Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695

Correspondence to Jason M. Haugh: jason_haugh{at}ncsu.edu

Migration of eukaryotic cells toward a chemoattractant often relies on their ability to distinguish receptor-mediated signaling at different subcellular locations, a phenomenon known as spatial sensing. A prominent example that is seen during wound healing is fibroblast migration in platelet-derived growth factor (PDGF) gradients. As in the well-characterized chemotactic cells Dictyostelium discoideum and neutrophils, signaling to the cytoskeleton via the phosphoinositide 3-kinase pathway in fibroblasts is spatially polarized by a PDGF gradient; however, the sensitivity of this process and how it is regulated are unknown. Through a quantitative analysis of mathematical models and live cell total internal reflection fluorescence microscopy experiments, we demonstrate that PDGF detection is governed by mechanisms that are fundamentally different from those in D. discoideum and neutrophils. Robust PDGF sensing requires steeper gradients and a much narrower range of absolute chemoattractant concentration, which is consistent with a simpler system lacking the feedback loops that yield signal amplification and adaptation in amoeboid cells.

Abbreviations used in this paper: AktPH, pleckstrin homology domain of Akt; GPCR, G protein–coupled receptor; OG, Oregon green; PI, phosphoinositide; TIRF, total internal reflection fluorescence.


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