Model of dendritic actin network with distributed turnover and structural remodeling*

The dendritic network of actin filaments provides the force for lamellipodial protrusions, driven by polymerization and branch generation by the Arp2/3 complex. Electron microscopy has revealed a network structure that varies with distance to the leading edge: a dense brushwork composed of short filaments near the leading edge is followed by longer and more linear filaments near the center and rear. Single molecule imaging experiments have shown that actin assembles throughout the lamellipodium and frequent disassembly within a few seconds after incorporation into the filament network. To investigate the mechanisms behind network remodeling, we created a three-dimensional stochastic model at the filament level that includes mechanisms for polymerization, depolymerization, branching, capping, uncapping, severing, oligomer diffusion, annealing, and debranching. We find that incorporating filament severing, enhanced near barbed ends, can explain the single molecule actin lifetime distribution and provide stable lamellipodia, as long as the oligomer fragments reanneal to free barbed or pointed ends with rate constants comparable to in vitro measurements. We thus propose a unified mechanism that fits a diverse set of basic lamellipodia phenomenology.