Involvement of Mechanical Strain in Actin Network Reorganization - Innovative Approaches to Cell Biomechanics - page 50

phalloidin and used to determine actin density is shown in Fig. 4.4a . Mean intensity
I center ( x ) was obtained as an average of normalized pixel intensity over the boxed
area in Fig. 4.4a , which corresponds to the analysis region illustrated in Fig. 4.3a .
For simplicity, I center ( x ) was normalized with the maximum pixel intensity, I center_max
of the analysis region.
A typical distribution of actin filament network density in the lamellipodia of fish
keratocytes is shown in Fig. 4.4b . It is evident that the density profile peaks at the
leading edge and then declines steadily toward the back of the lamellipodia. The
distribution profile confirms a well established fact that actin filaments at the lead-
ing edge of fish keratocytes is highly branched and polymerizes intensively to sus-
tain the remarkably fast migration of these cells. Interestingly, the reduction in
density toward the back of the lamellipodia clearly resembles the distribution of
compressive strain shown in Fig. 4.3b .

4.6.2 Correlating Mechanical Strain

and Actin Network Density

The distribution profile of actin network density in the lamellipodia is shown in
Fig. 4.4b . F-actin density peaks at the leading edge, and then decreases steadily
toward the back of the lamellipodium, in agreement with other reports (Svitkina
et al. 1997 ). Interestingly, the region of the lamellipodia where strain is predomi-
nantly negative correlates well with the region where F-actin density is markedly
low, as can be observed by comparing Figs. 4.3b and 4.4b .
Because a decrease in the actin filament density is a consequence of depolymeriza-
tion, the distribution suggests that negative strain could be involved in the depolymer-
ization of filament. Indeed tension release, which is what negative incremental strain
implies, has been shown by Sato et al. ( 2006 ) to induce disassembly of actin SFs.

4.6.3 Mechanism for Actin Network Reorganization

by Mechanical Strain

The orientation of actin filament with respect to the normal direction is denoted by
ʸ in Fig. 4.3a . The actual orientation angle of a single filament increases gradually
from ʸ ﾱ 35ﾰ at the leading edge to ʸ ﾱ 90ﾰ around the cell body (Svitkina et al.
1997 ). Here we attempt to explain the role of mechanical strain in the observed
change in actin filament orientation from the front to the back of the lamellipodia.
To explain the role of negative strain in actin network reorganization, a model
called “selective depolymerization model” has been proposed. The model proposes
that actin filaments depolymerize selectively depending on their orientation with
respect to negative strain, which is dominant in the migration direction. Thus, filaments
aligned in this direction are subjected to comparatively larger strain, and, as such,