Biomedical Engineering Reference
In-Depth Information
Accordingly, it is predicted that tension generated in the SFs leads to accumulation
of adhesion molecules, resulting in stronger adhesions capable of supporting higher
tensile forces (Buckley et al.
1998
). However, the paradox is that cells must also be
able to disassemble focal adhesion if they are to retract and move forward. In other
words, if they establish too strong adhesion bonds on the ECM, the expense in terms
of actomyosin tension required to disengage the bonds will be higher, thereby
impeding retraction. On the other hand, weak FAs may be insuffi cient to support the
generation of suffi cient tension necessary to pull the cell body and induce retraction.
Intriguingly, by mechanosensing and mechanotransduction, migrating cells are
capable of maintaining an optimal balance between intracellular tensile forces and
traction forces, which is crucial for coordinated migration. In fact, it is increasingly
become clear that attachment to the ECM allows intracellular forces to be transmitted
to the ECM and vice versa, and this is thought to be one of the underlying mechanism
by which cells detect the mechanical properties of the ECM and respond accordingly
(Chen
2008
; Riveline et al.
2001
; Solon et al.
2007
).
2.4
Development and Role of Traction Forces
in Cell Migration
2.4.1
Overview of Molecular Clutch Theory Proposed
for the Generation of Traction Forces
Several attempts have been made to elucidate the mechanism for the regulation of trac-
tion force generation by retrograde fl ow of actin network toward the back of the lamel-
lipodia (discussed in more detail in Chap.
3
)
. A “molecular clutch” hypothesis has been
suggested for the regulation of coupling interaction among actin fi laments and the
numerous proteins forming adhesion points. The theory suggests that adhesion mole-
cules can act as “clutches” that lock and unlock, and the degree or the functioning of
the clutches can regulate actin transport and traction force development (Aratyn-Schaus
and Gardel
2008
; Mitchison and Kirschner
1988
; Suter and Forscher
1998
).
According to this model, which is schematically illustrated in Fig.
2.6
, the assem-
bly of transmembrane proteins into complexes can create points of attachment
between the F-actin network and the immobile ECM. Thus, by regulating the degree
of mechanical coupling between the cytoskeletal F-actin network and the ECM, the
“molecular clutches” determine the relationship between retrograde fl ow and traction
forces. For example, as shown in Fig.
2.6
, when the clutch is engaged, tensile forces
originating from actomyosin contraction that could otherwise be used to generate
retrograde fl ow of actin fi laments network are transmitted to focal adhesion proteins
immobilized on the ECM. As a result, cells are able to exert traction forces against
the ECM (Aratyn-Schaus and Gardel
2008
). Consequently, retrograde fl ow will
