title: Actin filament elasticity and retrograde flow shape the force-velocity relation of motile cells.
abstract: Cells migrate through a crowded environment during processes such as metastasis or wound healing, and must generate and withstand substantial forces. The cellular motility responses to environmental forces are represented by their force-velocity relation, which has been measured for fish keratocytes but remains unexplained. Even pN opposing forces slow down lamellipodium motion by three orders of magnitude. At larger opposing forces, the retrograde flow of the actin network accelerates until it compensates for polymerization, and cell motion stalls. Subsequently, the lamellipodium adapts to the stalled state. We present a mechanism quantitatively explaining the cell's force-velocity relation and its changes upon application of drugs that hinder actin polymerization or actomyosin-based contractility. Elastic properties of filaments, close to the lamellipodium leading edge, and retrograde flow shape the force-velocity relation. To our knowledge, our results shed new light on how these migratory responses are regulated, and on the mechanics and structure of the lamellipodium.
authors.affiliation: Mathematical Cell Physiology, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. juliane.zimmermann@mdc-berlin.de
authors.forename: Juliane
authors.initials: J
authors.lastname: Zimmermann
authors.forename: Claudia
authors.initials: C
authors.lastname: Brunner
authors.forename: Mihaela
authors.initials: M
authors.lastname: Enculescu
authors.forename: Michael
authors.initials: M
authors.lastname: Goegler
authors.forename: Allen
authors.initials: A
authors.lastname: Ehrlicher
authors.forename: Josef
authors.initials: J
authors.lastname: Käs
authors.forename: Martin
authors.initials: M
authors.lastname: Falcke
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001696:Biomechanical Phenomena; D002465:Cell Movement / Q000187:drug effects; D060527:Corneal Keratocytes / Q000166:cytology; D015638:Cytochalasin D / Q000494:pharmacology; D004548:Elasticity / Q000187:drug effects; D006054:Goldfish; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D009281:Naphthalenes / Q000494:pharmacology
chemical_list: D001381:Azepines; D009281:Naphthalenes; C070571:ML 7; D015638:Cytochalasin D