Biomedical Engineering Reference
In-Depth Information
It will be revealed in the following sections that these assays are all planar
in nature, and currently no techniques exist which provide quantitative mea-
sures of cell adhesion in the native state of tissue resident cells (Garcia and
Gallant, 2003). Typically these cells are surrounded by and attached to rela-
tively soft (compared to glass or plastic) matrices in 3D (three-dimensions).
While mechanotransduction studies currently underway in numerous labora-
tories continue to address the effect of adhesive substrate mechanical prop-
erties on cell adhesion (Bershadsky
et al.
, 2006; Nicolas and Safran, 2006),
advancements in quantitative 3D methods and models will be necessary to
characterize the regulation of cell adhesion
in vivo
.
3.1.2 Cell motility: migration in response to biomaterials
Motility refers to the active mechanism of cellular movement in contrast
to diffusive or convective mechanisms. Cell motility is dependent on rapid
controlled changes in integrin-dependent cellular adhesion and plays a
key role in both normal physiology and disease (Ridley
et al.
, 2003; Stossel,
1993). In cellular locomotion, one end of the cell spreads while the other
retracts. Therefore this process may be considered to be a kind of polarized
cell spreading resulting from the continuous formation and disassembly
of adhesive structures. Motility is typically described as a three-step pro-
cess: protrusion, traction, and retraction (Mitchison and Cramer, 1996). In
response to a stimulus or as an interrogation of the microenvironment, a
lamellar protrusion is formed in the direction of the subsequent movement.
This protrusion, which is tightly coupled with actin polymerization, adheres
to the substrate. The cell body and nucleus then move forward over this
protrusion in a process known as traction, which involves the contraction
of actin and myosin cytoskeletal fi laments. The cytoplasm trailing behind
the cell body after movement is known as the tail. After traction occurs and
the cell body has moved forward, this tail de-adheres and retracts and the
process begins again (Mitchison and Cramer, 1996).
After reviewing cell adhesion assays, this chapter will examine assays that
have been employed to characterize cell migration in processes as diverse
as embryonic development, wound healing, tumor invasion and immune
response. The assays used to describe cell motility can also be divided into
two major categories (Table 3.2). The fi rst category includes approaches that
examine large populations of migrating cells over a prescribed period of time.
The second category consists of techniques that analyze the movements of
individual cells and directly quantify important movement parameters and
the effects of external stimuli on these parameters. Quantitative analyses of
cell motility that fall into this second category typically characterize speed,
persistence or directionality. Moreover, many of these assays have been
