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Review
. 2010:26:315-33.
doi: 10.1146/annurev.cellbio.011209.122036.

Mechanical integration of actin and adhesion dynamics in cell migration

Margaret L Gardel  1 , Ian C Schneider, Yvonne Aratyn-Schaus, Clare M Waterman
Affiliations
Review

Mechanical integration of actin and adhesion dynamics in cell migration

Margaret L Gardel et al. Annu Rev Cell Dev Biol. 2010.

Abstract

Directed cell migration is a physical process that requires dramatic changes in cell shape and adhesion to the extracellular matrix. For efficient movement, these processes must be spatiotemporally coordinated. To a large degree, the morphological changes and physical forces that occur during migration are generated by a dynamic filamentous actin (F-actin) cytoskeleton. Adhesion is regulated by dynamic assemblies of structural and signaling proteins that couple the F-actin cytoskeleton to the extracellular matrix. Here, we review current knowledge of the dynamic organization of the F-actin cytoskeleton in cell migration and the regulation of focal adhesion assembly and disassembly with an emphasis on how mechanical and biochemical signaling between these two systems regulate the coordination of physical processes in cell migration.

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Figures

Figure 1
Figure 1
Organization of the actomyosin cytoskeleton and adhesions in the leading edge of a migrating human osteosarcoma (U2OS) cell shown via double indirect immunolabeling of paxillin (red) and myosin light chain (MLC, blue) as well as fluorescent phalloidin staining of actin filaments (green). In each image the boxed area is shown magnified in the inset. (Upper left) The yellow dashed line highlights the lamellipodium-lamella border, and the asterisk highlights a junction between a dorsal stress fiber (DSF) and a transverse dorsal arc (TDA). NCA, network-contraction array; NA, nascent adhesion; FC, focal complex; FA, focal adhesion; MR, myosin II ribbon. In the merged image (lower right), the distal and proximal directions are highlighted.
Figure 2
Figure 2
Schematic diagram comparing the morphological phases of adhesion maturation (above, adhesion represented by purple ovals; length scales indicated are focal adhesion lengths) with the compositional phases of adhesion maturation (below, protein components listed) in response to increasing mechanical tension (gray arrow). At each of these steps, adhesion turnover can occur (curved black arrows) after a certain amount of time (timescale below each arrow). FAK, focal adhesion kinase; VASP, vasodilator-stimulated phosphoprotein.
Figure 3
Figure 3
Schematic diagram of the molecular clutch at the leading edge of a migrating cell. (a) The blue spheres are actin monomers assembling onto the barbed end of the actin filament (arrow) at the leading edge; dark brown bars are transmembrane integrins. (b) If the clutch is disengaged, the newly assembled actin (blue spheres), together with the action of myosin motors (yellow oval), drives the filament rearward, away from the leading edge in retrograde flow. (c) If the clutch is engaged, indirect interactions occur between actin-binding focal adhesion molecules (red) and integrin-binding focal adhesion molecules (green) to immobilize the filament. The forces of myosin on actin thus are transmitted through the focal adhesion into traction on the extracellular matrix, and new actin polymerization drives the leading edge forward in a protrusion.
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