Biomedical Engineering Reference
In-Depth Information
Chapter 8
Actomyosin Contractility Modulates
Lamellipodial Protrusion Dynamics
on a Micropatterned Substrate
Actin polymerization is believed to drive the protrusion of the lamellipodia, which
is the initial step during actin-based cell migration. This is closely followed by
attachment to the substrate which stabilizes the lamellipodia and enables forward
translocation of the cell body. This chapter introduces micropatterning technique,
which is a simple method for controlling cell adhesion. We outline the implementation
procedures and discuss how micropatterning can be utilized to explore the intimate
relationship between the three fundamental processes of cell migrations, i.e. protrusion,
retraction and adhesion. Furthermore, we discuss how the technique can be utilized
to investigate how cell-substrate interactions affect the protrusive dynamics of the
lamellipodia. The migration of fi sh keratocytes on micropatterned substrates
with varying lengths of non-adhesive gaps is considered, and an attempt is made to
correlate protrusion with actomyosin activity.
8.1
Introduction
As discussed in Chap.
1
, cells need to attach a substrate such as the extracellular cell
matrix (ECM) to be able to migrate. Attachment to a substrate is mediated by adhe-
sion proteins of the integrin superfamily, which are also linked to the actin cytoskel-
eton via vinculin and other associated adhesion proteins such as talin (also reviewed
in Chap.
1
)
. The mechanical linkage between integrin on the outside and actin cyto-
skeleton in the inside ensures that cues from the substrate are transmitted into the cell
where they are transduced into biochemical signals to direct intracellular activities,
including protrusion. In this way, cells can sense and respond to mechanical cues
emanating from the mechanical properties of the substrate, such as stiffness, topogra-
phy among others. Indeed, these cues are known to infl uence not only cell migration
but also differentiation, stemness etc., as discussed in more details in Chap.
11
.
In rapidly migrating cells such as epidermal fi sh keratocytes, lamellipodial pro-
trusion is driven by active polymerization at the leading edge. This process is known
