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Biophys. J. BioFAST: First Published August 5, 2005. doi:10.1529/biophysj.105.061564
© 2005 by the Biophysical Society.

A more recent version of this article appeared on October 1, 2005.
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CELL BIOPHYSICS

Distinguishing Modes of Eukaryotic Gradient Sensing

Ron Skupsky 1*, Wolfgang Losert 2 and Ralph J. Nossal 3

1 National Institutes of Health and University of Maryland
2 University of Maryland
3 National Institutes of Health

* To whom correspondence should be addressed. E-mail: skup{at}helix.nih.gov.

Submitted on February 24, 2005
Revised on April 19, 2005
Accepted on 17 June 2005


  Abstract
We develop a mathematical model of phosphoinositide-mediated gradient sensing which can be applied to chemotactic behavior in highly motile eukaryotic cells such as Dictyostelium and neutrophils. We generate four variants of our model by adjusting parameters that control the strength of coupled positive feedbacks and the importance of molecules that translocate from the cytosol to the membrane. Each variant exhibits a qualitatively different mode of gradient sensing. Simulations of characteristic behaviors suggest that differences between the variants are most evident at transitions between efficient gradient detection and failure. Based on these results, we propose criteria to distinguish between possible modes of gradient sensing in real cells, where many biochemical parameters may be unknown. We also identify constraints on parameters required for efficient gradient detection. Finally, our analysis suggests how a cell might transition between responsiveness and non-responsiveness, and between different modes of gradient sensing, by adjusting its biochemical parameters.

Key Words: cell signaling, chemotaxis, computer simulation, gradient sensing, mathematical modeling, phosphoinositides




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Copyright © 2005 by the Biophysical Society.