Biomedical Engineering Reference
In-Depth Information
Fig. 1
Cell adhesion to ECM components involves binding of integrin receptors. Fol-
lowing binding, integrins cluster, interact with the actin cytoskeleton, and form focal
adhesions, supramolecular complexes containing structural and signaling components.
Signals from focal adhesions regulate protein activity and gene expression (diagram,
left
).
Immunofluorescence staining (
right
) for cells spreading on FN (
blue
-DNA;
red
-F-actin
cytoskeleton;
green
-vinculin)
teins including FN and vitronectin, and these motifs often contain an acidic
amino acid. Ligand specificity is dictated by both subunits of a given
het-
erodimer, and in many instances individual integrins can bind to more than
one ligand (Table 1).
Integrin-mediated adhesion is a highly regulated process that involves re-
ceptor activation and mechanical coupling to extracellular ligands [4, 15, 16].
Integrins undergo conformational changes between high-affinity (“ON”) and
low-affinity (“OFF”) states that provide for spatial and temporal control of lig-
and binding activity. Following activation, bound receptors rapidly associate
with the actin cytoskeleton and cluster together to form focal adhesions, dis-
crete supramolecular complexes that contain structural proteins, such as vin-
culin, talin, and
αβ
-actinin, and signaling molecules, including FAK, Src, and
paxillin (Fig. 1) [17]. Interestingly, there are differences in the state of activa-
tion and components of focal adhesive structures, possibly reflecting different
functional complexes [18]. Focal adhesions are central elements in the ad-
hesion process, functioning as structural links between the cytoskeleton and
ECM to generate mechanical forces mediating stable adhesion, spreading, and
migration. Furthermore, in combination with growth factor receptors, focal
adhesions activate signaling pathways, such as MAPK and JNK, that regulate
transcription factor activity and direct cell cycle progression and differenti-
ation [6]. For example, binding of integrins
α
α
2
β
1
to COL-I
directs osteoblast cell survivial, proliferation, bone-specific gene expression,
and matrix mineralization [19-21].
α
5
β
1
to FN and
