Biomedical Engineering Reference
In-Depth Information
Table 2
Examples of interactions of some major ECM components via known binding
ECM component
Interaction/bound molecules
Collagen I
Self assembly, binding to integrin α 1 β 1 and α 2 β 1 , chondroitin and
dermatan sulfat, fibronectin, heparin
Collagen IV
Self assembly, binding to laminin, nidogen/entactin, perlecan,
α 1 β 1 integrin
Self assembly, nidogen/entactin,
α 1 β 1 integrin,
α 2 β 1 integrin,
α 3 β 1
α 6 β 1 integrin,
α 17 β 1 integrin,
α 6 β 4 integrin
Self assembly, fibrin, heparin sulfate, factor XIII, fibulin,
α 5 β 1 inte-
α 4 β 1 integrin,
α IIB β 3 integrin,
α V β 3 integrin, collagen, other
Heparan sulfate
Binding to a wide variety of growth factors including FGFs, BMPs,
collagen I
modified molecule. The unmasking of cryptic sites is a tightly controlled
process, reflecting the importance of cryptic ECM functions [31]. Exposure
of binding sites through conformational changes of ECM proteins directing
a sequential chain of binding steps was studied in detail for the formation
of fibronectin-fibronectin bonds. Self-assembly sites exposed upon applica-
tion of shear force on the protein when linked to integrin receptors was found
to be a most efficient working principle for the advanced control of matrix
reorganization and other processes [32]. Intriguing experimental and com-
putational data are emerging to suggest that mechanical forces regulate the
functional states of some proteins by stretching them into non-equilibrium
states. Molecular design principles were reported to control the exposure
of a protein's recognition sites, and/or their relative distances, in a force-
dependent manner [33].
The formation of supramolecular assemblies of ECM biopolymers defines
an obvious and highly important interconnection of physical and biospecific
characteristics of the matrices. In general, multiple specific interactions be-
tween individual biopolymers, such as collagen or fibronectin, result in the
formation of large fibrillar or meshwork-like structures segmenting tissues
and guiding cells by microstructural features and mechanical characteristics.
With those structures, often referred to as connective tissue, basement mem-
brane, and several others, the unique functionality of ECM and the fact that it
is based on both the provision of specific binding sites and physical forces is
best represented.
Another aspect of ECM related to both biospecific and physical character-
istics of ECM concerns the formation of gradients of any of the above-listed
signals to direct cellular behavior. Such gradients are, for instance, key to the
signalling of chemokines such as stromal cell-derived factor-1 (SDF-1) for the
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