Excitable actin dynamics in lamellipodial protrusion and retraction

Gillian L. Ryan, Heather M. Petroccia, Naoki Watanabe, Dimitrios Vavylonis

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

Many animal cells initiate crawling by protruding lamellipodia, consisting of a dense network of actin filaments, at their leading edge. We imaged XTC cells that exhibit flat lamellipodia on poly-L-lysine-coated coverslips. Using active contours, we tracked the leading edge and measured the total amount of F-actin by summing the pixel intensities within a 5-μm band. We observed protrusion and retraction with period 130-200 s and local wavelike features. Positive (negative) velocities correlated with minimum (maximum) integrated actin concentration. Approximately constant retrograde flow indicated that protrusions and retractions were driven by fluctuations of the actin polymerization rate. We present a model of these actin dynamics as an excitable system in which a diffusive, autocatalytic activator causes actin polymerization; F-actin accumulation in turn inhibits further activator accumulation. Simulations of the model reproduced the pattern of actin polymerization seen in experiments. To explore the model's assumption of an autocatalytic activation mechanism, we imaged cells expressing markers for both F-actin and the p21 subunit of the Arp2/3 complex. We found that integrated Arp2/3-complex concentrations spike several seconds before spikes of F-actin concentration. This suggests that the Arp2/3 complex participates in an activation mechanism that includes additional diffuse components. Response of cells to stimulation by fetal calf serum could be reproduced by the model, further supporting the proposed dynamical picture.

Original languageEnglish
Pages (from-to)1493-1502
Number of pages10
JournalBiophysical Journal
Volume102
Issue number7
DOIs
Publication statusPublished - 2012 Apr 4
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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