Biomedical Engineering Reference
In-Depth Information
Biospecific and Physical Characteristics of Extracellular Matrices
ECM variants found in different tissues and the current knowledge of their
structure-property relations are comprehensively summarized in several re-
views, periodicals and monographs [1-9]. The crucial role of ECM in any of
the most fundamental fate transitions of cells and in the development, main-
tenance and repair of tissues was demonstrated with a multitude of examples
as summarized in [10].
The discussion of ECM often uses the categorization of biospecific and
physical characteristics acting on the embedded cells. In that view biospe-
cific properties are directly related to molecular entities and their signalling
functions involved in cell adhesion, cell polarity, migration, proliferation, and
differentiation. Physical characteristics give rise to functions exceeding the
(inter)action of individual molecules governing cell scaffolding, the tensile
strength of tissues, cushioning (as in cartilage), filter functions (as in the
kidney), the formation of boundaries between, and within tissues, and the
storage of growth factors, cytokines, and chemokines. The use of these cat-
egories involves arbitrariness as seen by the fact that physical characteristics
of ECM often base on ensembles of biospecific bonds.
Biospecific signals of ECM concern the obvious role of the involved bio-
polymers to interact with molecular components of their environment in
precisely defined ways. The biological responses of cells to the ECM are reg-
ulated by specific cell-surface receptors. Many different receptors have been
identified that transduce signals including members of the heterodimeric
integrins, receptor tyrosine kinases and phosphatases, immunoglobulin su-
perfamily receptors, dystroglycan, and cell-surface proteoglycans. Most of
the biologically active ECM molecules, including laminins, collagens, throm-
bospondin, and fibronectin, contain multiple active sites, often for different
activities, and interact with different receptors. For example, some 40 active
sites have been identified on laminin-1 and 20 different receptors have been
characterized. In addition to that specific binding of ECM components in-
cludes the homo- and heteromolecular binding to other biopolymers of the
ECM leading to the formation of supramolecular assemblies (e.g. the forma-
tion of fibrils of collagen I and of co-fibrils of collagen I glycosaminoglycans),
the interaction with proteolytic enzymes, such as matrix metalloproteinases,
which cause the degradation of matrix biopolymers through catalyzing the
cleavage of certain bonds in the biopolymers' main chain, and the binding
of growth and differentiation factors as well as chemokines modulating the
presentation of theses molecules to the related cellular receptors via direct
binding of the ECM-bound factors or through their localized release.
Proteolytic cleavage of extracellular matrix (ECM) proteins by matrix met-
alloproteinases and/or conformational changes unmask “cryptic” sites and
liberate fragments with biological activities that are not observed in the un-
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