Modeling the synergy of cofilin and Arp2/3 in lamellipodial protrusive activity

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Rapid polymerization of actin filament barbed ends generates protrusive forces at the cell edge, leading to cell migration. Two important regulators of free barbed ends, cofilin and Arp2/3, have been shown to work in synergy (net effect greater than additive). To explore this synergy, we model the dynamics of F-actin at the leading edge, motivated by data from EGF-stimulated mammary carcinoma cells. We study how synergy depends on the localized rates and relative timing of cofilin and Arp2/3 activation at the cell edge. The model incorporates diffusion of cofilin, membrane protrusion, F-actin capping, aging, and severing by cofilin and branch nucleation by Arp2/3 (but not G-actin recycling). In a well-mixed system, cofilin and Arp2/3 can each generate a large pulse of barbed ends on their own, but have little synergy; high synergy occurs only at low activation rates, when few barbed ends are produced. In the full spatially distributed model, both synergy and barbed-end production are significant over a range of activation rates. Furthermore, barbed-end production is greatest when Arp2/3 activation is delayed relative to cofilin. Our model supports a direct role for cofilin-mediated actin polymerization in stimulated cell migration, including chemotaxis and cancer invasion.

Original languageEnglish (US)
Pages (from-to)1946-1955
Number of pages10
JournalBiophysical Journal
Volume105
Issue number9
DOIs
StatePublished - Nov 5 2013

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Actin Depolymerizing Factors
Actins
Polymerization
Cell Movement
Recycling
Chemotaxis
Actin Cytoskeleton
Epidermal Growth Factor
Breast Neoplasms
Membranes

ASJC Scopus subject areas

  • Biophysics

Cite this

Modeling the synergy of cofilin and Arp2/3 in lamellipodial protrusive activity. / Tania, Nessy; Condeelis, John S.; Edelstein-Keshet, Leah.

In: Biophysical Journal, Vol. 105, No. 9, 05.11.2013, p. 1946-1955.

Research output: Contribution to journalArticle

Tania, Nessy ; Condeelis, John S. ; Edelstein-Keshet, Leah. / Modeling the synergy of cofilin and Arp2/3 in lamellipodial protrusive activity. In: Biophysical Journal. 2013 ; Vol. 105, No. 9. pp. 1946-1955.
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