TY - JOUR A1 - Huber, Florian A1 - Käs, Josef A1 - Stuhrmann, Björn T1 - Growing actin networks form lamellipodium and lamellum by self-assembly JF - Biophysical Journal N2 - 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. KW - Open Archive Y1 - 2008 UR - http://www.ncbi.nlm.nih.gov/pubmed/18708450 U6 - https://doi.org/10.1529/biophysj.108.134817 SN - 1542-0086 VL - 95 IS - 12 SP - 5508 EP - 5523 PB - Biophysical Society ER - TY - JOUR A1 - Stuhrmann, Björn A1 - Huber, Florian A1 - Käs, Josef T1 - Robust organizational principles of protrusive biopolymer networks in migrating living cells JF - Plos One N2 - Cell migration is associated with the dynamic protrusion of a thin actin-based cytoskeletal extension at the cell front, which has been shown to consist of two different substructures, the leading lamellipodium and the subsequent lamellum. While the formation of the lamellipodium is increasingly well understood, organizational principles underlying the emergence of the lamellum are just beginning to be unraveled. We report here on a 1D mathematical model which describes the reaction-diffusion processes of a polarized actin network in steady state, and reproduces essential characteristics of the lamellipodium-lamellum system. We observe a steep gradient in filament lengths at the protruding edge, a local depolymerization maximum a few microns behind the edge, as well as a differential dominance of the network destabilizer ADF/cofilin and the stabilizer tropomyosin. We identify simple and robust organizational principles giving rise to the derived network characteristics, uncoupled from the specifics of any molecular implementation, and thus plausibly valid across cell types. An analysis of network length dependence on physico-chemical system parameters implies that to limit array treadmilling to cellular dimensions, network growth has to be truncated by mechanisms other than aging-induced depolymerization, e.g., by myosin-associated network dissociation at the transition to the cell body. Our work contributes to the analytical understanding of the cytoskeletal extension's bisection into lamellipodium and lamellum and sheds light on how cells organize their molecular machinery to achieve motility. KW - DOAJ Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:hbz:due62-opus-34901 SN - 1932-6203 N1 - Funding: This work has been supported by the Leipzig Graduate College ‘‘GK 1097 InterNeuro - Interdisciplinary Approaches in Cellular Neuroscience’’ (http:// www.uni-leipzig.de/˜ineuro/) and the Graduate School ‘‘Leipzig School of Natural Sciences - Building with Molecules and Nano-objects (BuildMoNa)’’ (http://www. buildmona.de/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. VL - 6 IS - 1 PB - Public Library of Science (PLoS) ER - TY - JOUR A1 - Smith, David A1 - Gentry, Brian A1 - Stuhrmann, Björn A1 - Huber, Florian A1 - Strehle, D. A.N. A1 - Brunner, Claudia A1 - Koch, Daniel A1 - Steinbeck, Matthias A1 - Betz, Timo A1 - Käs, Josef A. T1 - The cytoskeleton: An active polymer-based scaffold JF - Biophysical Reviews and Letters Y1 - 2009 U6 - https://doi.org/10.1142/S1793048009000983 SN - 1793-7035 VL - 04 SP - 179 EP - 208 ER -