A Continuum Model of Actin Waves in Dictyostelium discoideum

Varunyu Khamviwath,Hans G Othmer,Jifeng Hu,Pontus Aspenstrom

doi:10.1371/journal.pone.0064272

Abstract

Actin waves are complex dynamical patterns of the dendritic network of filamentous actin in eukaryotes. We developed a model of actin waves in PTEN-deficient Dictyostelium discoideum by deriving an approximation of the dynamics of discrete actin filaments and combining it with a signaling pathway that controls filament branching. This signaling pathway, together with the actin network, contains a positive feedback loop that drives the actin waves. Our model predicts the structure, composition, and dynamics of waves that are consistent with existing experimental evidence, as well as the biochemical dependence on various protein partners. Simulation suggests that actin waves are initiated when local actin network activity, caused by an independent process, exceeds a certain threshold. Moreover, diffusion of proteins that form a positive feedback loop with the actin network alone is sufficient for propagation of actin waves at the observed speed of . Decay of the wave back can be caused by scarcity of network components, and the shape of actin waves is highly dependent on the filament disassembly rate. The model allows retraction of actin waves and captures formation of new wave fronts in broken waves. Our results demonstrate that a delicate balance between a positive feedback, filament disassembly, and local availability of network components is essential for the complex dynamics of actin waves.

Highlights

Active cell movement is critical at various stages in the life cycle of most multicellular organisms, and movement entails force generation within cells and mechanical interactions with their surroundings
Because the F-actin structures associated with actin waves are restricted to cell regions close to the cortex, especially at the cellsubstrate interface, we assume that actin filaments only grow from the substrate-attached membrane of a cell placed on a flat surface
In this paper we presented a model of actin waves that incorporates filament dynamics and intracellular PI3 kinase (PI3K) signaling, which is essential for wave formation

Summary

Introduction

Active cell movement is critical at various stages in the life cycle of most multicellular organisms, and movement entails force generation within cells and mechanical interactions with their surroundings. We hypothesize that the feedback loop coupled with autocatalytic nucleation activity of existing filament barbed ends due to branching can serve as a basis for the spontaneous and sustained activity of actin waves, and we develop our model using the minimal necessary components of the feedback loop including Rac, WASP, and Arp2/3, that preserve this network structure.

Results

Conclusion