W. Richard Bowen and Nidal Hilal 4
W. Richard Bowen and Nidal Hilal 4
W. Richard Bowen and Nidal Hilal 4
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7.1 INTROdUCTION 197<br />
the cytoskeleton (Figure 7.1) (for background reading see, Alberts et al. [7]).<br />
The cell membrane is a barrier that separates the interior of the cell from<br />
the outside environment; it regulates the transport of molecules into <strong>and</strong><br />
out of the cell <strong>and</strong> maintains the interior of the cell at optimal levels of pH<br />
<strong>and</strong> ionic concentrations. Cell membranes are primarily made of a selectively<br />
permeable lipid bilayer, containing various functional proteins that<br />
are involved in a range of specific cellular activities. For example, 25–50%<br />
of membrane receptors may be adhesive receptors [8]. The interior compartment<br />
next to the cell membrane is the cytoplasm. This accommodates<br />
a number of specialised subcellular organelles that cooperate to maintain<br />
cell function. The cytoskeleton, which is located within the cytoplasm, is<br />
made up of three types of long rod-shaped molecules: microfilaments (e.g.<br />
actin stress fibre), microtubules (e.g. tubulin) <strong>and</strong> intermediate filaments<br />
(e.g. vimentin). These molecules attach to one another, link to other subcellular<br />
systems, such as the cell membrane <strong>and</strong> cell nucleus, <strong>and</strong> build<br />
a framework to give the cell both shape <strong>and</strong> movement. The configuration<br />
of the cytoskeleton dynamically adapts during cellular processes <strong>and</strong><br />
undergoes microscopically observable morphological changes.<br />
It is now clear that a particular family of transmembrane cell surface<br />
receptors, the integrins, mediate many of the interactions between a cell<br />
<strong>and</strong> the ECM. They both recognise peptide sequences, such as Arg-Gly-Asp<br />
(RGD) within the chains of certain ECM proteins (e.g. fibronectin), <strong>and</strong><br />
connect the cytoskeleton to the ECM. During this process, adhesive<br />
contacts between the cell <strong>and</strong> the ECM are formed [9]. A common type<br />
of adhesive contact involves multiprotein complexes, called focal adhesions.<br />
These comprise integrins, the associated cytoplasmic proteins,<br />
<strong>and</strong> a number of protein kinases [1, 10]. Focal adhesions are the major<br />
sites for actin stress fibre attachment <strong>and</strong> thus a connection between the<br />
cytoskeleton <strong>and</strong> the ECM. Integrins that are bound to the ECM transmit<br />
Nucleus<br />
Focal adhesion<br />
Cell membrane<br />
F-actin stress fibre<br />
Direction of motion<br />
ECM or substrate<br />
Microtubule<br />
Filopodium<br />
Pseudopodium<br />
Lamellopodium<br />
FIgurE 7.1 Schematic drawing of cell adhesion to an ECM or substrate. The cell<br />
adheres firmly to the ECM through focal adhesions (a multiprotein complex). The focal<br />
adhesions are the sites for the attachment of F-actin stress fibres – one type of cytoskeleton<br />
protein. Filopodium <strong>and</strong> lamellopodium are located at the leading edge for cell to migrate.