Load adaptation of lamellipodial actin networks Journal Article


Author(s): Mueller, Jan; Szep, Gregory; Nemethova, Maria; de Vries, Ingrid; Lieber, Arnon D; Winkler, Christoph; Kruse, Karsten; Small, John V; Schmeiser, Christian; Keren, Kinneret; Hauschild, Robert; Sixt, Michael
Article Title: Load adaptation of lamellipodial actin networks
Affiliation IST Austria
Abstract: Actin filaments polymerizing against membranes power endocytosis, vesicular traffic, and cell motility. In vitro reconstitution studies suggest that the structure and the dynamics of actin networks respond to mechanical forces. We demonstrate that lamellipodial actin of migrating cells responds to mechanical load when membrane tension is modulated. In a steady state, migrating cell filaments assume the canonical dendritic geometry, defined by Arp2/3-generated 70° branch points. Increased tension triggers a dense network with a broadened range of angles, whereas decreased tension causes a shift to a sparse configuration dominated by filaments growing perpendicularly to the plasma membrane. We show that these responses emerge from the geometry of branched actin: when load per filament decreases, elongation speed increases and perpendicular filaments gradually outcompete others because they polymerize the shortest distance to the membrane, where they are protected from capping. This network-intrinsic geometrical adaptation mechanism tunes protrusive force in response to mechanical load.
Journal Title: Cell
Volume: 171
Issue 1
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2017-09-21
Start Page: 188
End Page: 200
DOI: 10.1016/j.cell.2017.07.051
Notes: We thank the scientific support facilities of IST Austria and Biocenter Vienna for technical support and CP Heisenberg for fish lines. This work was supported by the European Research Council (ERC StG 281556), a grant from the Austrian Science Foundation (FWF) (to M.S.), and a grant from Vienna Science and Technology Fund (WWTF) (No. LS13-029 to C.S. and M.S.). Research in the lab of K. Keren was supported by a grant from the United States-Israel Binational Science Foundation (No. 2013275 with Alex Mogilner).
Open access: no