Inhomogeneities in 3D Collagen Matrices Impact Matrix Mechanics and Cancer Cell Migration

Hayn, Alexander; Fischer, Tony; Mierke, Claudia Tanja

doi:10.3389/fcell.2020.593879

Cited by 34 publications

(35 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both collagens were mixed in a mass ratio of 1:2 (rat/bovine), as we have employed this collagen mixture previously to explore the effect of ILK on the migration and invasion of cells ( Kunschmann et al, 2017 ). This distinct combination of collagens is chosen as it provides a rather homogenous network that is capable to mimic the in vivo scaffold of connective tissue ( Hayn et al, 2020 ). To explore the effect of PINCH1 on fibroblast migration and invasion we determined the migratory ability of PINCH1 knockout (PINCH1 −/− ) and PINCH1 wild-type (PINCH1 fl/fl ) fibroblasts by placing each on dense 3D extracellular matrices (with a thickness of approximately 500 μm and a collagen concentration of 3.0 g/l) and allowing them to invade ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

PINCH1 Promotes Fibroblast Migration in Extracellular Matrices and Influences Their Mechanophenotype

Mierke

Hayn

Fischer

2022

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

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 knock-out 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.

show abstract

Section: Resultsmentioning

confidence: 99%

PINCH1 Promotes Fibroblast Migration in Extracellular Matrices and Influences Their Mechanophenotype

Mierke

Hayn

Fischer

2022

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…For measurements, cells were prepared as described previously 40 , 41 . Briefly, about 24 h prior to the measurement, cells were seeded onto 35 mm culture dishes (about 10 5 cells per dish).…”

Section: Methodsmentioning

confidence: 99%

“…Average quantities were then derived as the population average from all cells measured across these multiple samples. For J 0 , the average was calculated as the geometric average, while for β the arithmetic average was used 40 , 41 .…”

Section: Methodsmentioning

confidence: 99%

Cell mechanical properties of human breast carcinoma cells depend on temperature

Aermes

Hayn

Fischer

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

The knowledge of cell mechanics is required to understand cellular processes and functions, such as the movement of cells, and the development of tissue engineering in cancer therapy. Cell mechanical properties depend on a variety of factors, such as cellular environments, and may also rely on external factors, such as the ambient temperature. The impact of temperature on cell mechanics is not clearly understood. To explore the effect of temperature on cell mechanics, we employed magnetic tweezers to apply a force of 1 nN to 4.5 µm superparamagnetic beads. The beads were coated with fibronectin and coupled to human epithelial breast cancer cells, in particular MCF-7 and MDA-MB-231 cells. Cells were measured in a temperature range between 25 and 45 °C. The creep response of both cell types followed a weak power law. At all temperatures, the MDA-MB-231 cells were pronouncedly softer compared to the MCF-7 cells, whereas their fluidity was increased. However, with increasing temperature, the cells became significantly softer and more fluid. Since mechanical properties are manifested in the cell’s cytoskeletal structure and the paramagnetic beads are coupled through cell surface receptors linked to cytoskeletal structures, such as actin and myosin filaments as well as microtubules, the cells were probed with pharmacological drugs impacting the actin filament polymerization, such as Latrunculin A, the myosin filaments, such as Blebbistatin, and the microtubules, such as Demecolcine, during the magnetic tweezer measurements in the specific temperature range. Irrespective of pharmacological interventions, the creep response of cells followed a weak power law at all temperatures. Inhibition of the actin polymerization resulted in increased softness in both cell types and decreased fluidity exclusively in MDA-MB-231 cells. Blebbistatin had an effect on the compliance of MDA-MB-231 cells at lower temperatures, which was minor on the compliance MCF-7 cells. Microtubule inhibition affected the fluidity of MCF-7 cells but did not have a significant effect on the compliance of MCF-7 and MDA-MB-231 cells. In summary, with increasing temperature, the cells became significant softer with specific differences between the investigated drugs and cell lines.

show abstract

“…Interestingly, ECM-induced EMT correlates with TGFβ activation by resident epithelial cells. Also, the inhomogeneity of 3D environments may promote clustered cells to switch to a single cell-dominated invasion [ 92 ]. Conversely, denser substrates and decreased porosity would lead to the opposite switch, from individual to collective cell migration.…”

Section: Probe Of Biophysical Stimulimentioning

confidence: 99%

Unravelling cell migration: defining movement from the cell surface

Merino-Casallo

Gómez‐Benito

Hervas-Raluy

et al. 2022

Cell Adhesion & Migration

View full text Add to dashboard Cite

Cell motility is essential for life and development. Unfortunately, cell migration is also linked to several pathological processes, such as cancer metastasis. Cells’ ability to migrate relies on many actors. Cells change their migratory strategy based on their phenotype and the properties of the surrounding microenvironment. Cell migration is, therefore, an extremely complex phenomenon. Researchers have investigated cell motility for more than a century. Recent discoveries have uncovered some of the mysteries associated with the mechanisms involved in cell migration, such as intracellular signaling and cell mechanics. These findings involve different players, including transmembrane receptors, adhesive complexes, cytoskeletal components , the nucleus, and the extracellular matrix. This review aims to give a global overview of our current understanding of cell migration.

show abstract

Inhomogeneities in 3D Collagen Matrices Impact Matrix Mechanics and Cancer Cell Migration

Cited by 34 publications

References 66 publications

PINCH1 Promotes Fibroblast Migration in Extracellular Matrices and Influences Their Mechanophenotype

PINCH1 Promotes Fibroblast Migration in Extracellular Matrices and Influences Their Mechanophenotype

Cell mechanical properties of human breast carcinoma cells depend on temperature

Unravelling cell migration: defining movement from the cell surface

Contact Info

Product

Resources

About