Cell migration performs a critical function in numerous physiological processes, including
tissue homeostasis or wound healing after tissue injury, as well as pathological processes
that include malignant progression of cancer. The efficiency of cell migration and invasion
appears to be based on the mechano-phenotype of the cytoskeleton. The properties of
the cytoskeleton depend on internal cytoskeletal and external environmental factors. A
reason for this are connections between the cell and its local matrix microenvironment,
which are established by cell-matrix adhesion receptors. Upon activation, focal adhesion
proteins such as PINCH1 are recruited to sites where focal adhesions form. PINCH1
specifically couples through interactions with ILK, which binds to cell matrix receptors and
the actomyosin cytoskeleton. However, the role of PINCH1 in cell mechanics regulating
cellular motility in 3D collagen matrices is still unclear. PINCH1 is thought to facilitate 3D
motility by regulating cellular mechanical properties, such as stiffness. In this study,
PINCH1 wild-type and knock-out cells were examined for their ability to migrate in
dense extracellular 3D matrices. Indeed, PINCH1 wild-type cells migrated more
numerously and deeper in 3D matrices, compared to knock-out cells. Moreover,
cellular deformability was determined, e.g., elastic modulus (stiffness). PINCH1 knockout
cells are more deformable (compliable) than PINCH1 wild-type cells. Migration of both
PINCH1−/− cells and PINCH1fl/fl cells was decreased by Latrunculin A inhibition of actin
polymerization, suggesting that actin cytoskeletal differences are not responsible for the
discrepancy in invasiveness of the two cell types. However, the mechanical phenotype of
PINCH1−/− cells may be reflected by Latrunculin A treatment of PINCH1fl/fl cells, as they
exhibit resembling deformability to untreated PINCH1−/− cells. Moreover, an apparent
mismatch exists between the elongation of the long axis and the contraction of the short
axis between PINCH1fl/fl cells and PINCH1−/− cells following Latrunculin A treatment. There
is evidence of this indicating a shift in the proxy values for Poisson’s ratio in PINCH1−/− cells
compared with PINCH1fl/fl cells. This is probably attributable to modifications in
cytoskeletal architecture. The non-muscle myosin II inhibitor Blebbistatin also reduced
the cell invasiveness in 3D extracellular matrices but instead caused a stiffening of the cells.
Finally, PINCH1 is apparently essential for providing cellular mechanical stiffness through
the actin cytoskeleton, which regulates 3D motility.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:86358 |
| Date | 03 July 2023 |
| Creators | Mierke, Claudia Tanja, Hayn, Alexander, Fischer, Tony |
| Publisher | Frontiers Media |
| 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, 869563 |
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