Growing actin networks form lamellipodium and lamellum by self-assembly.
Many different cell types are able to migrate by formation of a thin actin-based cytoskeletal extension. Recently, it became evident that this extension consists of two distinct substructures, designated lamellipodium and lamellum, which differ significantly in their kinetic and kinematic properties as well as their biochemical composition. We developed a stochastic two-dimensional computer simulation that includes chemical reaction kinetics, G-actin diffusion, and filament transport to investigate the formation of growing actin networks in migrating cells. Model parameters were chosen based on experimental data or theoretical considerations. In this work, we demonstrate the system's ability to form two distinct networks by self-organization. We found a characteristic transition in mean filament length as well as a distinct maximum in depolymerization flux, both within the first 1-2 microm. The separation into two distinct substructures was found to be extremely robust with respect to initial conditions and variation of model parameters. We quantitatively investigated the complex interplay between ADF/cofilin and tropomyosin and propose a plausible mechanism that leads to spatial separation of, respectively, ADF/cofilin- or tropomyosin-dominated compartments. Tropomyosin was found to play an important role in stabilizing the lamellar actin network. Furthermore, the influence of filament severing and annealing on the network properties is explored, and simulation data are compared to existing experimental data.
Huber
Florian
F
Institute of Soft Matter Physics, University of Leipzig, Leipzig, Germany. florian.huber@uni-leipzig.de
Käs
Josef
J
Stuhrmann
Björn
B
D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D005399:Fishes / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D011554:Pseudopodia / Q000737:chemistry* / Q000378:metabolism*; D015203:Reproducibility of Results
D000199:Actins