A temporal model of cofilin regulation and the early peak of actin barbed ends in invasive tumor cells

Nessy Tania, Erin Prosk, John S. Condeelis, Leah Edelstein-Keshet

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Cofilin is an important regulator of actin polymerization, cell migration, and chemotaxis. Recent experimental data on mammary carcinoma cells reveal that stimulation by epidermal growth factor (EGF) generates a pool of active cofilin that results in a peak of actin filament barbed ends on the timescale of 1 min. Here, we present results of a mathematical model for the dynamics of cofilin and its transition between several pools in response to EGF stimulation. We describe the interactions of phospholipase C, membrane lipids (PIP2), and cofilin bound to PIP2 and to F-actin, as well as diffusible cofilin in active G-actinmonomer-bound or phosphorylated states. We consider a simplified representation in which the thin cell edge (lamellipod) and the cell interior are represented by two compartments that are linked by diffusion. We demonstrate that a high basal level of active cofilin stored by binding to PIP2, as well as the highly enriched local milieu of F-actin at the cell edge, is essential to capture the EGF-induced barbed-end amplification observed experimentally.

Original languageEnglish (US)
Pages (from-to)1883-1892
Number of pages10
JournalBiophysical Journal
Volume100
Issue number8
DOIs
StatePublished - Apr 20 2011
Externally publishedYes

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Actin Depolymerizing Factors
Actins
Epidermal Growth Factor
Neoplasms
Type C Phospholipases
Chemotaxis
Membrane Lipids
Actin Cytoskeleton
Polymerization
Cell Movement
Theoretical Models
Breast Neoplasms

ASJC Scopus subject areas

  • Biophysics

Cite this

A temporal model of cofilin regulation and the early peak of actin barbed ends in invasive tumor cells. / Tania, Nessy; Prosk, Erin; Condeelis, John S.; Edelstein-Keshet, Leah.

In: Biophysical Journal, Vol. 100, No. 8, 20.04.2011, p. 1883-1892.

Research output: Contribution to journalArticle

Tania, Nessy ; Prosk, Erin ; Condeelis, John S. ; Edelstein-Keshet, Leah. / A temporal model of cofilin regulation and the early peak of actin barbed ends in invasive tumor cells. In: Biophysical Journal. 2011 ; Vol. 100, No. 8. pp. 1883-1892.
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