title: A minimal actomyosin-based model predicts the dynamics of filopodia on neuronal dendrites.
abstract: Dendritic filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the filopodia is crucial for synaptogenesis, but the underlying mechanisms are poorly understood. To study filopodial motility, we collected and analyzed image data on filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity, and substrate adhesion gives rise to various filopodial behaviors. We formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility, and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls dendritic filopodia dynamics.
authors.affiliation: R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Olena O
authors.initials: OO
authors.lastname: Marchenko
authors.affiliation: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, New York, NY 10461.
authors.forename: Sulagna
authors.initials: S
authors.lastname: Das
authors.affiliation: R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Ji
authors.initials: J
authors.lastname: Yu
authors.affiliation: R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Igor L
authors.initials: IL
authors.lastname: Novak
authors.affiliation: R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Rodionov
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Nadia
authors.initials: N
authors.lastname: Efimova
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Svitkina
authors.affiliation: Departments of Physics and Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Wolgemuth
authors.affiliation: R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06030 les@volt.uchc.edu.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Loew
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D008870:Microtubules / Q000378:metabolism; D008958:Models, Molecular; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011554:Pseudopodia / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000205:Actomyosin