title: A continuum model of actin waves in Dictyostelium discoideum.
abstract: Actin waves are complex dynamical patterns of the dendritic network of filamentous actin in eukaryotes. We developed a model of actin waves in PTEN-deficient Dictyostelium discoideum by deriving an approximation of the dynamics of discrete actin filaments and combining it with a signaling pathway that controls filament branching. This signaling pathway, together with the actin network, contains a positive feedback loop that drives the actin waves. Our model predicts the structure, composition, and dynamics of waves that are consistent with existing experimental evidence, as well as the biochemical dependence on various protein partners. Simulation suggests that actin waves are initiated when local actin network activity, caused by an independent process, exceeds a certain threshold. Moreover, diffusion of proteins that form a positive feedback loop with the actin network alone is sufficient for propagation of actin waves at the observed speed of * 6 mm/min. Decay of the wave back can be caused by scarcity of network components, and the shape of actin waves is highly dependent on the filament disassembly rate. The model allows retraction of actin waves and captures formation of new wave fronts in broken waves. Our results demonstrate that a delicate balance between a positive feedback, filament disassembly, and local availability of network components is essential for the complex dynamics of actin waves.
authors.affiliation: School of Mathematics, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Varunyu
authors.initials: V
authors.lastname: Khamviwath
authors.forename: Jifeng
authors.initials: J
authors.lastname: Hu
authors.forename: Hans G
authors.initials: HG
authors.lastname: Othmer
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000378:metabolism / Q000648:ultrastructure*; D004023:Dictyostelium / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D008853:Microscopy; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism / Q000648:ultrastructure*; D015398:Signal Transduction; D059008:Time-Lapse Imaging; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D054378:Acetogenins
chemical_list: D015107:4-Butyrolactone; D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D024462:Myosin Type II; D051059:PTEN Phosphohydrolase; D015800:Protozoan Proteins; D051316:Wiskott-Aldrich Syndrome Protein; D020744:rac GTP-Binding Proteins; C438920:coronin acetogenin; D054378:Acetogenins