Document Type

Article

Publication Date

5-1-2008

Publication Title

Biophysical Journal

Abstract

We have developed a top-down, rule-based mathematical model to explore the basic principles that coordinate mechanochemical events during animal cell migration, particularly the local-stimulation-global-inhibition model suggested originally for chemotaxis. Cells were modeled as a shape machine that protrudes or retracts in response to a combination of local protrusion and global retraction signals. Using an optimization algorithm to identify parameters that generate specific shapes and migration patterns, we show that the mechanism of local stimulation global inhibition can readily account for the behavior of Dictyosteliumunder a large collection of conditions. Within this collection, some parameters showed strong correlation, indicating that a normal phenotype may be maintained by complementation among functional modules. In addition, comparison of parameters for control and nocodazole-treated Dictyostelium identified the most prominent effect of microtubules as regulating the rates of retraction and protrusion signal decay, and the extent of global inhibition. Other changes in parameters can lead to profound transformations from amoeboid cells into cell smimicking keratocytes, neurons, or fibroblasts. Thus, a simple circuit of local stimulation-global inhibition can account for a wide range of cell behaviors. A similar top-down approachmay be applied to other complex problems and combined with molecular manipulations to de. ne specific protein functions.

Volume

94

Issue

9

First Page Number

3671

Last Page Number

3683

DOI

10.1529/biophysj.107.117002

Publisher Statement

© 2008, Biophysical Society. Available on publisher's site at http://dx.crossref.org/10.1529%2Fbiophysj.107.117002.

Included in

Mathematics Commons

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