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William Holmes
Last active: 2/26/2016

Regimes of wave type patterning driven by refractory actin feedback: transition from static polarization to dynamic wave behaviour.

Holmes WR, Carlsson AE, Edelstein-Keshet L
Phys Biol. 2012 9 (4): 046005

PMID: 22785332 · PMCID: PMC3414641 · DOI:10.1088/1478-3975/9/4/046005

Patterns of waves, patches, and peaks of actin are observed experimentally in many living cells. Models of this phenomenon have been based on the interplay between filamentous actin (F-actin) and its nucleation promoting factors (NPFs) that activate the Arp2/3 complex. Here we present an alternative biologically-motivated model for F-actin-NPF interaction based on properties of GTPases acting as NPFs. GTPases (such as Cdc42, Rac) are known to promote actin nucleation, and to have active membrane-bound and inactive cytosolic forms. The model is a natural extension of a previous mathematical mini-model of small GTPases that generates static cell polarization. Like other modellers, we assume that F-actin negative feedback shapes the observed patterns by suppressing the trailing edge of NPF-generated wave-fronts, hence localizing the activity spatially. We find that our NPF-actin model generates a rich set of behaviours, spanning a transition from static polarization to single pulses, reflecting waves, wave trains, and oscillations localized at the cell edge. The model is developed with simplicity in mind to investigate the interaction between nucleation promoting factor kinetics and negative feedback. It explains distinct types of pattern initiation mechanisms, and identifies parameter regimes corresponding to distinct behaviours. We show that weak actin feedback yields static patterning, moderate feedback yields dynamical behaviour such as travelling waves, and strong feedback can lead to wave trains or total suppression of patterning. We use a recently introduced nonlinear bifurcation analysis to explore the parameter space of this model and predict its behaviour with simulations validating those results.

MeSH Terms (9)

Actin-Related Protein 2-3 Complex Actin Cytoskeleton Actins Animals Computer Simulation Humans Models, Biological Protein Interaction Maps rho GTP-Binding Proteins

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