An Autocatalytic Activator-Inhibitor Model of Actin Polymerization at the Leading Edge of Fibroblast Lamellipodia

Abstract

Crawling animal cells are driven by lamellipodia -- thin, dynamic, sheet-like projections consisting of a dense network of branched actin filaments. Arp2/3 complex mediated actin polymerization near the leading edge drives protrusion required for cellular motility. Actin filaments polymerize near the leading edge and undergo retrograde flow towards the main body of the cell. Both random fluctuations and travelling waves of protrusion and retraction have been observed during cell spreading. To characterize the protrusion rates of XTC fibroblasts we use active contours to track the leading edge of cells. We then calculate the correlation between local actin and Arp2/3 complex accumulation and cell protrusion rate as measured from conventional fluorescent microscopy. We also use quantitative fluorescent speckle microscopy, which allows us to track the dynamics of individual proteins within the actin network and measure quantities such as the retrograde flow rate. We present a noise-driven model of these actin-mediated protrusion events in which a diffusive, autocatalytic activator mediates actin polymerization, while actin saturation in turn inhibits further activator accumulation. Using analytic theory we find that our model captures both excitable and oscillatory behaviors, and can be tuned between the two behaviors by adjusting model parameters. Using computer simulation we are able to produce patterns of actin polymerization that are quantitatively similar to those observed along the leading edge in live cell experiments.