Regulation of Actin Cytoskeleton Dynamics in Migrating Cells - Innovative Approaches to Cell Biomechanics - page 12

Coupling
interactions

Actin network
dynamics

Mechanical factors

Contractile forces
Traction forces
Tension/strain

Polymerization
Depolymerization
Network flow

Cell migration

Fig. 2.1 Relationship between actin network dynamics, mechanical factors and cell migration
( Okeyo et al. 2010 ). Cell migration is regulated by coupling interactions among mechanical and
biochemical factors (mechanochemical coupling) (Adapted with permission from JSME: [Journal
of Biomechanical Science and Engineering], copyright (2012))

motility are introduced, and their roles in the spatiotemporal regulation of actin
network dynamics during cell motility are reviewed. Specifi cally, the contribution
of regulatory factors, both mechanical and biochemical, to the regulation of key
events involved in actin network dynamics by polymerization and depolymerization,
and the mechanism proposed for the net transport of actin network by retrograde
fl ow and anterograde fl ow are discussed.

2.2 Biochemical Regulation of Actin Network Dynamics

in Lamellipodia

2.2.1 Protein Interactions Involved in Actin Network Assembly

The fl exibility and adaptability of the actin cytoskeleton to its key function of
driving cell motility is maintained by a host of functionally specialized proteins that
bind and interact with the actin fi laments (Fig. 2.2a ). Actin polymerization is the
result of a concerted regulation by a set of regulatory proteins at the leading edge
that carefully determine the pace and spatial organization of the assembly process
(Le Clainche and Carlier 2008 ). These molecular regulators include Arp2/3, profi lin,
formins, and capping proteins, just to mention a few. Among them, Arp2/3 is the
best studied, and it is known to be a stable complex of seven conserved subunits,
including actin-related proteins Arp2 and Arp3, and ARPC1, ARPC2, ARPC3,
ARPC4, and ARPC5 (Goley and Welch 2006 ). The complex localizes at the leading
edge of the lamellipodia where it nucleates new fi laments from preexisting ones,
resulting in an interconnected and a branched 2D network (dendritic network, Fig. 2.2a )
(Iwasa and Mullins 2007 ).
Arp2/3 is activated by Wiskott-Aldrich syndrome protein (WASP) downstream
of other regulatory proteins such as Cdc42 and Rac1 (Goley and Welch 2006 ).
WASP can also be stimulated directly by mechanical stimuli originating from the