W. Richard Bowen and Nidal Hilal 4

7.1 INTROdUCTION 197
the cytoskeleton (Figure 7.1) (for background reading see, Alberts et al. [7]).
The cell membrane is a barrier that separates the interior of the cell from
the outside environment; it regulates the transport of molecules into and
out of the cell and maintains the interior of the cell at optimal levels of pH
and ionic concentrations. Cell membranes are primarily made of a selectively
permeable lipid bilayer, containing various functional proteins that
are involved in a range of specific cellular activities. For example, 25–50%
of membrane receptors may be adhesive receptors [8]. The interior compartment
next to the cell membrane is the cytoplasm. This accommodates
a number of specialised subcellular organelles that cooperate to maintain
cell function. The cytoskeleton, which is located within the cytoplasm, is
made up of three types of long rod-shaped molecules: microfilaments (e.g.
actin stress fibre), microtubules (e.g. tubulin) and intermediate filaments
(e.g. vimentin). These molecules attach to one another, link to other subcellular
systems, such as the cell membrane and cell nucleus, and build
a framework to give the cell both shape and movement. The configuration
of the cytoskeleton dynamically adapts during cellular processes and
undergoes microscopically observable morphological changes.
It is now clear that a particular family of transmembrane cell surface
receptors, the integrins, mediate many of the interactions between a cell
and the ECM. They both recognise peptide sequences, such as Arg-Gly-Asp
(RGD) within the chains of certain ECM proteins (e.g. fibronectin), and
connect the cytoskeleton to the ECM. During this process, adhesive
contacts between the cell and the ECM are formed [9]. A common type
of adhesive contact involves multiprotein complexes, called focal adhesions.
These comprise integrins, the associated cytoplasmic proteins,
and a number of protein kinases [1, 10]. Focal adhesions are the major
sites for actin stress fibre attachment and thus a connection between the
cytoskeleton and the ECM. Integrins that are bound to the ECM transmit
Nucleus
Focal adhesion
Cell membrane
F-actin stress fibre
Direction of motion
ECM or substrate
Microtubule
Filopodium
Pseudopodium
Lamellopodium
FIgurE 7.1 Schematic drawing of cell adhesion to an ECM or substrate. The cell
adheres firmly to the ECM through focal adhesions (a multiprotein complex). The focal
adhesions are the sites for the attachment of F-actin stress fibres – one type of cytoskeleton
protein. Filopodium and lamellopodium are located at the leading edge for cell to migrate.