Biomedical Engineering Reference
In-Depth Information
endothelial, and muscle cells as well as provide immobilized ligands for cell
surface receptors [70]. The supramolecular organization of collagen type IV
is facilitated by different association sites of the collagen monomers resulting
in the formation of dimers, tetramers, and lateral supertwisted associations
stabilized by covalent bonds [71]. However, the proposed meshwork model
of collagen IV [72] cannot explain the fine network of the basement mem-
brane in tissues. Consequently, the concept of enmeshed laminin and colla-
gen type IV polymers is the currently accepted model [73]. Various studies
have shown that collagen type IV reassembles under physiological condi-
tions in vitro. Interaction of laminin and collagen IV, both isolated from the
Engelbreth-Holm-Swarm tumor, under physiological conditions were found
to result in the precipitation of the basement membrane molecules while
collagen alone gave no precipitate indicating that the components of the base-
ment membrane interact in a highly specific manner [74]. However, later
studies revealed that collagen type IV isolated from bovine lens capsules
and from human placenta can construct the skeletal meshwork observed in
the lamina densa under physiological conditions without addition of other
macromolecules [75]. Interestingly, the reconstituted collagen type IV ag-
gregates actually provided dimensionally similar geometries in comparison
to collagen IV lattices which were seen in the lamina densa of the mouse
pancreas.
Collagen IV/laminin matrices are widely used in cell culture studies. For
example, phenotypic changes of human umbilical endothelial vein cells were
analyzed with respect to the formation of a network of tubular structures with
intercellular or lumen-like spaces. Ultrastructural analyses of the capillary-
like structures and the mechanism of lumen-like formation indicated that the
in vivo angiogenesis was better reproduced in the collagen IV/laminin model
matrix as compared to the addition of FGF to the culture medium [76]. In
vivo, these gels are used for measuring angiogenic inhibitors and stimula-
tors, to improve graft survival and to repair various damaged tissues [77]. For
example, liquid bioartificial tissue substitutes based on collagen IV/laminin
containing embryonic stem cells were furthermore reported to constitute
a powerful new approach to restoring injured heart muscle without distorting
its geometry and structure [78].
The formation of fibronectin fibrils, another relatively well-studied supra-
molecular structure of ECM polymers, was extensively studied in vitro
as well. Many different cell types synthesize fibronectin and secrete it as
a disulfide-bonded dimer composed of 230-270 kDa subunits. Each sub-
unit contains three types of repeating modules, types I, II, and III. These
modules comprise functional domains that mediate interactions with other
ECM components, with cell surface receptors and with fibronectin itself. Fi-
bronectin matrix assembly involves binding domains and repeating modules
from all regions of fibronectin which participate in interactions with cell
surface receptors and with other fibronectin molecules. Newly secreted fi-
