Biomedical Engineering Reference
In-Depth Information
Fig. 2 Contact area between lower cell membrane and substrate surface forming the cell-surface
junction. Adhesion is provided by cell-surface receptors that specifically bind to components of
the ECM pre-adsorbed upon the substrate surface (adapted from [ 12 ])
Both subunits share a hydrophobic domain, which spans the cell membrane, and
rather small cytosolic C-terminal domains. On the intracellular side, the b-subunit
of the integrins is linked to the actin cytoskeleton [ 13 , 14 ] by means of cytoskeletal
adapter proteins (Fig. 2 ), such as talin, vinculin, a-actinin and paxillin. In contrast
to all other integrins, the a 6 b 4 integrin associates with the keratin intermediate
filaments (hemi-desmosomes). Thus, integrins interconnect the intracellular protein
filaments of the cytoskeleton with the protein filaments of the ECM and serve
as a transmembrane bridge between these two macromolecular networks (Fig. 2 ),
providing mechanical stability to the cell-surface junction. The distribution of
integrins in the plasma membrane of adherent cells is very often not homogeneous.
After ligand binding, they tend to cluster locally, forming so-called focal adhesions
or focal contacts [ 1 , 15 ]. At these adhesion sites, the cells are believed to have the
closest distance to the surface.
Depending on their subunit composition, integrins differ significantly with
respect to their specificity for different ECM proteins. Molecular recognition and
binding of individual ECM proteins are generally mediated by rather short amino
acid sequences (*4 - 10 amino acids) within the primary structure of ECM
proteins. The most well-known amino acid sequence involved in integrin recog-
nition is the tetrapeptide binding motif Arg-Gly-Asp-Ser (RGDS), a sequence
found in many ECM ligands including the ECM proteins fibronectin and vitro-
nectin [ 14 , 16 ]. Many integrins are multispecific receptors, meaning that they can
bind several different ECM proteins as long as these carry a suitable recognition
sequence. On the other hand, one particular ECM protein may interact with various
integrins by carrying more than one recognition sequence in its primary structure.
Apart from their crucial functional role in cell adhesion and linkage of the
cytoskeleton to the ECM [ 10 ], integrins act as bi-directional signaling receptors
that
mediate
information
transfer
across
the
plasma
membrane
and
thereby
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