Biomedical Engineering Reference
In-Depth Information
Polymerization
force
Retrograde
flow
Myosin
motors
F-actin
Network
tensile forces
Molecular
clutch
ECM
ECM
compliance
Molecular
clutch
(disengaged)
Molecular
clutch
(engaged)
Integrin
Fig. 2.6
Schematic representation of mechanical coupling between F-actin and ECM (Okeyo
et al.
2010
). Molecular clutches that determine the cytoskeleton-ECM coupling are represented as
extensible springs. The number of molecular clutches in the engaged position (
dotted red box
)
determine the degree of coupling and therefore retrograde velocity and traction force.
Dotted blue
box
shows disengaged position (Adapted with permission from JSME: [Journal of Biomechanical
Science and Engineering], copyright (2012))
decrease while the rate of protrusion will increase because actin polymerization will
now make a greater contribution to this process (Jurado et al.
2005
).
Conversely, if the clutch is disengaged, slippage will occur between the cytoskeletal
and adhesion receptors, thus increasing retrograde fl ow while simultaneously
decreasing the rate of protrusion, since increased retrograde fl ow will limit the effi -
ciency of protrusion by subtracting newly polymerized actin from the leading edge
(Jurado et al.
2005
). Moreover, the decrease in mechanical coupling that accompany
clutch disengagement will reduce the amount of force transmittable to the ECM,
resulting in reduced traction force.
For a given adhesion molecule to function as a clutch, it should be able to link
both an actin fi lament and the intracellular domain of integrins. In this respect,
vinculin and talin are thought to be suitable candidates for a molecular clutch
because they can bind both F-actin and integrins (Li et al.
2005
; Horwitz et al.
1986
;
Hu et al.
2007
). Indeed, studies using correlation fl uorescent speckle microscopy
have quantitatively measured the coupling of focal adhesion proteins to actin fi laments
and demonstrated that the motion of talin and vinculin that bind both integrins and
F-actin is more consistent with F-actin fl ow than is the motion of integrins which
are, in most cases, immobilized on the ECM (Hu et al.
2007
).
