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as the elastic modulus, is a metric reflective of the stiffness of a material.
Although stiffness and the elastic modulus are not identical, for the case of
unconstrained uniaxial tension or compression, it can be considered a mea-
sure of the stiffness of a material. The elastic modulus of filopodia is twice
than that of the lamellipodium, which is characterized by a meshwork of
actin filaments (
Xiong et al., 2009
). Moreover, the actin filament enriched
peripheral domain, taken as a whole (lamellipodia and filopodia), exhibits
greater stiffness relative to the central domain. The filopodium thus repre-
sents a relatively stiffer cellular subdomain than the rest of the growth cone.
Advancing growth cones generate pulling forces on the substratum
(
Lamoureux et al., 1989
). Filopodia extend outward from the surface of the
cell and are eventually retracted back into the cell. As discussed in Sections
4.3 and 4.4
, the retraction of filopodia is partially driven by myosin II activ-
ity. Myosin II is a contractile mechanoenzyme that contributes to cellular
contractility in nonmuscle cells by acting on actin filaments. The contact
of a filopodium with another cell, or a noncellular object, can result in the
pulling on the contacted surface by the filopodium (
Kress et al., 2007
).
The force generated by a single growth cone filopodium undergoing con-
traction has been estimated to be on the order of 50-90 µdyn (
Heide-
mann et al., 1990
). Filopodia from myosin IIB knockout neurons exhibit
decreased traction force
(Bridgman et al., 2001)
, consistent with a myosin
II-based contractile mechanism. Growth cone filopodial traction forces are
considered to be determined by the engagement of myosin II-dependent
retrograde flow with “clutches” formed by the interactions of the filopo-
dium with the substratum (
Chan and Odde, 2008
). Individual filopodia
from the same growth cone exhibit significant variations in the amplitude
of force generation and slippage of the clutches (
Chan and Odde, 2008
),
consistent with reported interfilopodial differences in the rate of retrograde
flow (
Mallavarapu and Mitchison, 1999
). The pulling of filopodia may con-
tribute to the forward advance of the growth cone. However, inhibition of
myosin II (
Turney and Bridgman, 2005
;
Ketschek et al., 2007
), disruption
of actin filaments (Section
2.2
), or depletion of filopodia in vivo (
Dwivedy
et al., 2007
) affects the rate of growth cone advance in a cell type and/or
extracellular environment-dependent manner, and the effects are at least
in part attributable to the role of myosin II in regulating the advance of
microtubules in the growth cone (
Ketschek et al., 2007
; see Section
5
).
In conclusion, it seems unlikely that pulling by filopodia is an absolute
requirement of growth cone advance, but it may contribute in some
contexts.
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