title: A growth factor-induced, spatially organizing cytoskeletal module enables rapid and persistent fibroblast migration.
abstract: Directional migration requires robust front/back polarity. We find that fibroblasts treated with platelet-derived growth factor (PDGF) and prepolarized by plating on a fibronectin line substrate exhibit persistent migration for hours. This does not occur in the absence of PDGF or on uniformly coated fibronectin substrates. Persistent migration arises from establishment of two functional modules at cell front and back. At the front, formation of a zone containing podosome-like structures (PLS) dynamically correlates with low RhoA and myosin activity and absence of a contractile lamella. At the back, myosin contractility specifically controls tail retraction with minimal crosstalk to the front module. The PLS zone is maintained in a dynamic steady state that preserves size and position relative to the cell front, allowing for long-term coordination of front and back modules. We propose that front/back uncoupling achieved by the PLS zone is crucial for persistent migration in the absence of directional cues.
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.
authors.forename: Katrin
authors.initials: K
authors.lastname: Martin
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, LHRRB 301B, Boston, MA 02115, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Vilela
authors.affiliation: School of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Noo Li
authors.initials: NL
authors.lastname: Jeon
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, LHRRB 301B, Boston, MA 02115, USA.
authors.forename: Gaudenz
authors.initials: G
authors.lastname: Danuser
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland. Electronic address: olivier.pertz@unibas.ch.
authors.forename: Olivier
authors.initials: O
authors.lastname: Pertz
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005353:Fibronectins / Q000494:pharmacology; D009218:Myosins / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats
chemical_list: D005353:Fibronectins; D010982:Platelet-Derived Growth Factor; D009218:Myosins