Regulation of Actin Cytoskeleton Dynamics in Migrating Cells - Innovative Approaches to Cell Biomechanics - page 18

Verkhovsky et al. 1999 ). This interaction causes filament bending and network
contraction (Fig. 2.4c ), resulting in the network being deformed compressively.
We discuss the importance of this deformation on actin fi lament dynamics in
Chap. 4 . In addition, actomyosin interaction causes fi lament realignment, mainly in
the cell interior away from the leading edge (Fig. 2.4c , middle). As a result, toward
the cell body, fi laments become more oriented parallel to the leading edge, as
reported for fi sh keratocytes (Svitkina et al. 1997 ) (Fig. 2.4a, c ). As mentioned
already in Sect. 2.1 , actin fi laments at the back of the lamellipodia are further
bundled by

-actinin and other cross-linking proteins, including myosin II to
form stress fi bers (SFs) (Pellegrin and Mellor 2007 ). SFs interact with non-muscle
myosin II motors to generate tensile forces necessary for cell body translocation,
adhesion dynamics and retraction (Anderson et al. 1996 ; Svitkina et al. 1997 ;
Kolega 1986 ). In polarized fast locomoting cells like keratocytes, SFs are in the
form of transverse arcs (Fig. 2.4a ) that enable them to generate forward directed
force for cell body translocation (Svitkina et al. 1997 ; Burton et al. 1999 ). They are
strategically localized at the boundary between lamellipodia and the cell body
(Fig. 2.4a ) so as to maximize the utilization of contractile forces for cell body trans-
location and retraction.

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2.3.3 Correlating Intracellular Mechanical Forces

with Traction Forces

At the leading edge, polymerization is coupled with adhesion, since fi lament-ECM
bond is required to prevent backward sliding of polymerizing actin fi laments,
which otherwise would decrease polymerization effi ciency (Borisy and Svitkina 2000 ).
In fact, as illustrated in Fig. 2.5a , the front region of the lamellipodia is dotted with
small adhesions that generate rearward oriented, propulsive traction forces (Oliver
et al. 1999 ). Moreover, it has been demonstrated that adhesion maturation at the
leading edge of migrating cells requires tension in the actin cytoskeleton (Puklin-
Faucher and Sheetz 2009 ).
Similarly, at the contractile module, both ends of stress fi bers (SFs) must be
fi rmly anchored via focal adhesions (FAs) to the ECM in order to generate tensile
forces (Fig. 2.5a ) (Burridge et al. 1987 ; Hotulainen and Lappalainen 2006 ). Even
rapidly moving cells such as fi sh keratocytes that are weakly adhered to the ECM still
possess particularly large FAs at the lateral edges that anchor SFs to the ECM to
facilitate contractile force generation (Fig. 2.5a ). This category of FAs has been
associated with inwardly oriented pinching traction forces that correlate with
contractile forces along the SFs (Fig. 2.5b ) (Oliver et al. 1999 ; Burton et al. 1999 ).
Overall, studies using different cell types have shown that the integrity of actin
cytoskeleton, particularly SFs depends on adhesion (Goffi n et al. 2006 ;
ChrzanowskaWodnicka and Burridge 1996 ). Moreover, it has been noted that traction