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Formation of transient lamellipodia

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Item Type:Article
Title:Formation of transient lamellipodia
Creators Name:Zimmermann, J. and Falcke, M.
Abstract:Cell motility driven by actin polymerization is pivotal to the development and survival of organisms and individual cells. Motile cells plated on flat substrates form membrane protrusions called lamellipodia. The protrusions repeatedly appear and retract in all directions. If a lamellipodium is stabilized and lasts for some time, it can take over the lead and determine the direction of cell motion. Protrusions traveling along the cell perimeter have also been observed. Their initiation is in some situations the effect of the dynamics of the pathway linking plasma membrane receptors to actin filament nucleation, e.g. in chemotaxis. However, lamellipodia are also formed in many cells incessantly during motion with a constant state of the signaling pathways upstream from nucleation promoting factors (NPFs), or spontaneously in resting cells. These observations strongly suggest protrusion formation can also be a consequence of the dynamics downstream from NPFs, with signaling setting the dynamic regime but not initiating the formation of individual protrusions. A quantitative mechanism for this kind of lamellipodium dynamics has not been suggested yet. Here, we present a model exhibiting excitable actin network dynamics. Individual lamellipodia form due to random supercritical filament nucleation events amplified by autocatalytic branching. They last for about 30 seconds to many minutes and are terminated by filament bundling, severing and capping. We show the relevance of the model mechanism for experimentally observed protrusion dynamics by reproducing in very good approximation the repetitive protrusion formation measured by Burnette et al. with respect to the velocities of leading edge protrusion and retrograde flow, oscillation amplitudes, periods and shape, as well as the phase relation between protrusion and retrograde flow. Our modeling results agree with the mechanism of actin bundle formation during lamellipodium retraction suggested by Burnette et al. and Koestler et al.
Keywords:Actins, Biological Models, Pseudopodia, Animals
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science (U.S.A.)
Volume:9
Number:2
Page Range:e87638
Date:5 February 2014
Official Publication:https://doi.org/10.1371/journal.pone.0087638
PubMed:View item in PubMed

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