Introduction to Actin-Based Cell Migration - Innovative Approaches to Cell Biomechanics - page 2

all undergo movement by protruding the cell front and retracting the rear. In fact,
front-rear polarity is an important initial step during cell migration.
Cell migration is a complex cell function mediated by macromolecular proteins
that form the cell cytoskeleton. These proteins are capable of self-assembly and
dynamic turnover to generate forces for cell movement. Protrusion at the cell front
and retraction at the rear involves structural reorganization of the actin cytoskeleton
and focal adhesions, respectively. Although intensive research over the last 20 years
has shed light into the molecular players and pathways involved in cell migration,
precisely how cells regulate the many molecular and structural dynamics that take
place at different cellular modules during cell movement is less understood (Rafelski
and Theriot 2004 ). In fact, the complexity of cell migration lies in the fact that
different processes occur simultaneously and involve numerous coupling interactions
among mechanical and biochemical factors (Kim et al. 2009 ).
In this chapter, we undertake a general and broad background review of cell
motility. We highlight the major cellular components involved in cell motility and
the fundamental processes of cell migration, based on keratocytes and fragments
derived from them.

1.2 Steps Involved in Cell Migration

Cell migration can be regarded as a multistep mechanical process involving a series
of complex but spatiotemporally well coordinated processes, including protrusion
of the leading edge (Borisy and Svitkina 2000 ; Pollard and Borisy 2003 ), attachment
to the substrate via focal adhesions (FAs) (Palecek et al. 1997 ), and retraction of
the cell rear (Chen 1981 ).
Cell movement begins when localized actin polymerization leads to the protrusion
of the plasma membrane to form a specialized protrusive structure known as a
lamellipodium or a fi lopodium depending on shape. Most migrating cell types,
including fi sh keratocytes shown in Fig. 1.1a , form a wide and fl at protrusive structure
called a lamellipodium. However, some cells like the neuronal growth cones form a
narrow and fi nger-like structure known as a fi lopodium. Since the fundamental
processes are the same for both lamellipodia-based and fi lopodia-based migration,
we base our discussion on the lamellipodia.
The vital steps of cell migration are summarized in Fig. 1.1b . The fi rst step
involves protrusion of the lamellipodium Fig. 1.1b-2 , which results in cell polariza-
tion and determines the direction of migration. In the second step, the protruding
lamellipodium attaches to the substrate via specialized transmembrane structures
known as focal adhesions (FAs) (Fig. 1.1b-3 ) (Burridge and Fath 1989 ). By anchor-
ing the actin cytoskeleton to the substrate, FAs provide a platform for cytoskeletal
force generation, in addition to supporting continuous polymerization and protru-
sion of the leading edge.