Biomedical Engineering Reference
In-Depth Information
Thus, in the case of calyculin, increased contractility due to actomyosin activation
results in increased SF tension and network contraction thereby leading to increased
retrograde flow intensity (Figs.
5.2a
and
5.3
). Concomitantly, increased contractility
would result in increased retraction and cell body translocation, with associated
increase in the intensity of anterograde flow of F-actin network (Fig.
5.2a
). Conversely,
inhibiting actomyosin contractility by blebbistatin would result in a reduction in the
intensity of both retrograde and anterograde (compare Figs.
5.2c
and
5.3
).
Although the two flows eventually merge in the interior of the lamellipodia, it
remains to be clarified whether this convergence occurs passively or actively (in the
sense of being driven by localized actomyosin interaction). Overall, the observed
effects of actomyosin perturbation on F-actin flow suggest that actomyosin contrac-
tion drives actin network dynamics, in agreement with previous reports (Verkhovsky
et al.
1999
; Henson et al.
1997
; Svitkina et al.
1997
).
Furthermore, quantitative analysis of F-actin network deformation in the lamellipo-
dia of migrating fish keratocytes shows that F-actin network compressive deformation
is significantly negative in the parallel direction (Fig.
5.4
). As pointed out previously
(Adachi et al.
2009
), the negative nature of the obtained strain rate would result from
anisotropic network contraction generated by actomyosin contractility along the trans-
verse SF bundles (Kolega
2006
; Verkhovsky et al.
1999
; Svitkina et al.
1997
).
Moreover, increase in deformation magnitude toward the back of the lamellipo-
dia where myosin II is more abundant, as observed in the case of calyculin
(Fig.
5.4c
), confirms that the contractile module at the back of the lamellipodia
generates the forces that cause network deformation. Thus, the deformation can be
regarded as a direct consequence of actomyosin contractility, mainly along the con-
tractile SF bundles.
As expected, the F-actin network would undergo compressive deformation by
virtue of being sandwiched between two opposing flows. In fact, the convergence
of retrograde and anterograde flows at the interior of the lamellipodia (Fig.
5.2a, b
)
is associated with a steep change in the gradient of flow velocity, which can con-
tribute significantly to the computed negative strain rate, as highlighted in
Fig.
5.4a
.
Overall, the results actomyosin perturbation on network deformation described
here supports the contribution of actin network flow convergence to network contrac-
tion and depolymerization, as suggested previously (Vallotton et al.
2004
; Ponti et al.
2005
). However, it should be noted that the continuum-based approach to strain anal-
ysis presented here is not capable of computing network deformation at the level of a
single filament. This is a task for simulation studies using molecular dynamics.
5.7
Self-Regulatory Mechanism of the Actin Cytoskeleton
In Chap.
4
, we proposed the selective depolymerization model for the involve-
ment of negative strain in the depolymerization and reorganization of F-actin.
Here, we describe a proposed pathway illustrated in Fig.
5.5
for the
