Biomedical Engineering Reference
In-Depth Information
(compressive strain) may induce depolymerization is by stimulating ADF/cofilin
and other biochemical factors that regulate F-actin depolymerization and severing,
as reported elsewhere (Svitkina et al.
1997
; Hayakawa et al.
2003
; McCullough
et al.
2008
).
The argument for the existence of selective depolymerization of filaments can be
extended further to explain the observed changes in filament orientation from the
leading edge (ilaments are oriented at ~35 οΎ° to the leading edge) toward the back of
the lamellipodia (filaments are oriented normal to migration direction). One possi-
bility is that strain induced depolymerization helps to create more room for the
rotation of filaments by myosin II sliding along divergent F-actins (Schaub et al.
2007
). Evidence for depolymerization is clear from the observed decrease in actin
density at the back of the lamellipodia (Fig.
4.4b
), implying that re-alignment is
concomitant with depolymerization.
There is little doubt that contractile forces generated by actomyosin interactions
are involved in causing actual filament realignment and network deformation
(Svitkina et al.
1997
; Schaub et al.
2007
). In other words, the contractile machinery
at the back of lamellipodia generates contractile forces that cause network deforma-
tion and retrograde flow (Verkhovsky et al.
1999
; Svitkina et al.
1997
). Moreover, it
is important to mention that negative (compressive) strain is just one among the
many factors that may contribute to spatiotemporal regulation of the actin structure.
To suffice, the selective depolymerization model described here compliments the
dynamic network contraction model (Svitkina et al.
1997
) in explaining the role of
contractility in actin network reorganization. Chapter
5
will discuss the mechanism
of network deformation based on the experimental results looking at actomyosin
contractility in migrating fish keratocytes.
4.7
Conclusion
This chapter has presented experimental methods for quantitatively evaluating the
strain field in the actin filament network forming the lamellipodia of migrating fish
keratocytes. In order to elucidate the mechanism by which actin filament network
reorganization is regulated by biomechanical factors.
The results highlight the existence of a negative (compressive) strain in the
lamellipodia whose direction is parallel to that of cell movement. A close correla-
tion has been found between the distributions of the strain and the actin filament
density in the lamellipodia, suggesting that negative strain, in the form of tension
release, may play a role in the depolymerization filament.
Based on this result, selective depolymerization model has been proposed, which
postulates that negative strain couples with biomechanical factors such as ADF/
cofilin to promote selective depolymerization of those filaments oriented in the
direction of the deformation. This is because such filaments are, by virtue of their
orientation, subjected to comparatively higher levels of compressive deformation.
This model, in conjunction with network contraction model, may be used to explain
