Cell motility under physiological and pathological conditions including malignant
progression of cancer and subsequent metastasis are founded on environmental
confinements. During the last two decades, three-dimensional cell migration has been
studied mostly by utilizing biomimetic extracellular matrix models. In the majority of
these studies, the in vitro collagen scaffolds are usually assumed to be homogenous,
as they consist commonly of one specific type of collagen, such as collagen type I,
isolated from one species. These collagen matrices should resemble in vivo extracellular
matrix scaffolds physiologically, however, mechanical phenotype and functional reliability
have been addressed poorly due to certain limitations based on the assumption
of homogeneity. How local variations of extracellular matrix structure impact matrix
mechanics and cell migration is largely unknown. Here, we hypothesize that local
inhomogeneities alter cell movement due to alterations in matrix mechanics, as they
frequently occur in in vivo tissue scaffolds and were even changed in diseased tissues.
To analyze the effect of structural inhomogeneities on cell migration, we used a mixture
of rat tail and bovine dermal collagen type I as well as pure rat and pure bovine collagens
at four different concentrations to assess three-dimensional scaffold inhomogeneities.
Collagen type I from rat self-assembled to elongated fibrils, whereas bovine collagen
tended to build node-shaped inhomogeneous scaffolds. We have shown that the
elastic modulus determined with atomic force microscopy in combination with pore size
analysis using confocal laser scanning microscopy revealed distinct inhomogeneities
within collagen matrices. We hypothesized that elastic modulus and pore size govern
cancer cell invasion in three-dimensional collagen matrices. In fact, invasiveness of three
breast cancer cell types is altered due to matrix-type and concentration indicating that
these two factors are crucial for cellular invasiveness. Our findings revealed that local
matrix scaffold inhomogeneity is another crucial parameter to explain differences in
cell migration, which not solely depended on pore size and stiffness of the collagen
matrices. With these three distinct biophysical parameters, characterizing structure
and mechanics of the studied collagen matrices, we were able to explain differences
in the invasion behavior of the studied cancer cell lines in dependence of the used
collagen model.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84507 |
| Date | 03 April 2023 |
| Creators | Hayn, Alexander, Fischer, Tony, Mierke, Claudia Tanja |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2296-634X, 593879 |
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