A role for actin arcs in the leading-edge advance of migrating cells.

National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature Cell Biology (Impact Factor: 20.06). 03/2011; 13(4):371-81. DOI: 10.1038/ncb2205
Source: PubMed

ABSTRACT Epithelial cell migration requires coordination of two actin modules at the leading edge: one in the lamellipodium and one in the lamella. How the two modules connect mechanistically to regulate directed edge motion is not understood. Using live-cell imaging and photoactivation approaches, we demonstrate that the actin network of the lamellipodium evolves spatio-temporally into the lamella. This occurs during the retraction phase of edge motion, when myosin II redistributes to the lamellipodial actin and condenses it into an actin arc parallel to the edge. The new actin arc moves rearward, slowing down at focal adhesions in the lamella. We propose that net edge extension occurs by nascent focal adhesions advancing the site at which new actin arcs slow down and form the base of the next protrusion event. The actin arc thereby serves as a structural element underlying the temporal and spatial connection between the lamellipodium and the lamella during directed cell motion.

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    ABSTRACT: We are grateful to Falko Ziebert and Igor Aranson, who continue with their comment on our publication [5] a discussion on modelling concepts. Ziebert and Aranson present in their contribution to this volume [14] a model concept for cell motility and morphodynamics focusing on gel flow and its determinants. This type of models is particularly useful for describing slow dynamics on the length scale of the whole cell and modelling of cell shape [1,8,11,13,14]. Our approach is set apart from the gel models by taking into account a weakly cross-linked F-actin network region close to the location of polymerization in the lamellipodia of motile cells (semi-flexible region) in addition to the gel in the bulk. This addition explains a variety of non-linear dynamic regimes in cellular and reconstituted systems, and the force-velocity relation of fish keratocytes. Ziebert and Aranson point out in their comment that 1) a more detailed modelling of gel processes may be required to capture large cell deformations, 2) the dynamics of adhesion strength and distribution may be relevant for understanding the relation between cell shape, the dynamic regime of motion and cell velocity, 3) coarse grained models may allow for unifying both concepts, and 4) fluctuations are important in morphodynamics.
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    ABSTRACT: The forces experienced by filaments in actin based propulsion in reconstituted systems and cell motility, the mechanical properties of the lamellipodium of motile cells due to filament branching and cross-linking, the free filament contour length between branch points, the mechanisms of the force-velocity relation and velocity oscillations are all topics of ongoing debate. Here, we review results with a modelling concept considering the F-actin network as weakly cross-linked in a region with dynamic depth close to the propelled obstacle and gel-like further back. It offers quantitative explanations for steady motion and oscillation mechanisms in reconstituted systems and motile cells, and the force-velocity relation of fish keratocytes.
    The European Physical Journal Special Topics 06/2014; 223(7):1353-1372. · 1.76 Impact Factor

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