title: Nano-scale actin-network characterization of fibroblast cells lacking functional Arp2/3 complex.
abstract: Arp2/3 complex is thought to be the primary protrusive force generator in cell migration by controlling the assembly and turnover of the branched filament network that pushes the leading edge of moving cells forward. However, mouse fibroblasts without functional Arp2/3 complex migrate at rates similar to wild-type cells, contradicting this paradigm. We show by correlative fluorescence and large-scale cryo-tomography studies combined with automated actin-network analysis that the absence of functional Arp2/3 complex has profound effects on the nano-scale architecture of actin networks. Our quantitative analysis at the single-filament level revealed that cells lacking functional Arp2/3 complex fail to regulate location-dependent fine-tuning of actin filament growth and organization that is distinct from its role in the formation and regulation of dendritic actin networks.
authors.affiliation: Bioinformatics and Structural Biology Program, Sanford-Burnham Medical Research Institute, La Jolla, CA, United States.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Anderson
authors.affiliation: Bioinformatics and Structural Biology Program, Sanford-Burnham Medical Research Institute, La Jolla, CA, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Page
authors.affiliation: Bioinformatics and Structural Biology Program, Sanford-Burnham Medical Research Institute, La Jolla, CA, United States.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Swift
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, MD, United States.
authors.forename: Praveen
authors.initials: P
authors.lastname: Suraneni
authors.affiliation: Bioinformatics and Structural Biology Program, Sanford-Burnham Medical Research Institute, La Jolla, CA, United States.
authors.forename: Mandy E W
authors.initials: MEW
authors.lastname: Janssen
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, United States; Department of Cell Biology and of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Pollard
authors.affiliation: Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, MD, United States.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Bioinformatics and Structural Biology Program, Sanford-Burnham Medical Research Institute, La Jolla, CA, United States. Electronic address: niels@burnham.org.
authors.forename: Niels
authors.initials: N
authors.lastname: Volkmann
authors.affiliation: Bioinformatics and Structural Biology Program, Sanford-Burnham Medical Research Institute, La Jolla, CA, United States. Electronic address: dorit@burnham.org.
authors.forename: Dorit
authors.initials: D
authors.lastname: Hanein
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002478:Cells, Cultured; D020285:Cryoelectron Microscopy; D055032:Electron Microscope Tomography; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins
keywords: Actin networks; Correlative imaging; Large-scale cellular cryo-tomography; Quantitative automated analysis