Intermediate filaments ensure resiliency of single carcinoma cells, while active contractility of the actin cortex determines their invasive potential

Abstract

During the epithelial-to-mesenchymal transition, the intracellular cytoskeleton undergoes severe reorganization which allows epithelial cells to transition into a motile mesenchymal phenotype. Among the different cytoskeletal elements, the intermediate filaments keratin (in epithelial cells) and vimentin (in mesenchymal cells) have been demonstrated to be useful and reliable histological markers. In this study, we assess the potential invasiveness of six human breast carcinoma cell lines and two mouse fibroblasts cells lines through single cell migration assays in confinement. We find that the keratin and vimentin networks behave mechanically the same when cells crawl through narrow channels and that vimentin protein expression does not strongly correlate to single cells invasiveness. Instead, we find that what determines successful migration through confining spaces is the ability of cells to mechanically switch from a substrate-dependent stress fibers based contractility to a substrate-independent cortical contractility, which is not linked to their tumor phenotype.

Effect of non-linear strain stiffening in eDAH and unjamming

“…Mesenchymal MDA-MB-436 cells did not pass through the narrow constrictions. 53 The highly squeezed MDA-MB-436 cells are too rigid to pass through the constriction.…”

Microfluidic Lab-on-a-Chip for Studies of Cell Migration under Spatial Confinement

“…In addition to the micrometer size of the constraints and the tailoring of their geometry, this approach allows for a high-resolution imaging of the migrating cells thanks to the thin and transparent device floor. This micro-constriction configuration has been used for more systematic biological studies such as the adaptability of different cancer cell lines (MCF-10, MDA-MB-231) to micro-constrained environments and to study different migration behaviors depending on cancer cell invasiveness [ 29 , 30 ].…”

“…Once they reach the bloodstream, cells may experience confinement as they navigate through vessels of 3–4 m diameter [ 17 , 18 ]. Such confined migration induces significant structural changes in the cell’s cytoskeleton [ 29 , 30 ] and focal adhesions while also affecting the nuclear shape and the distribution of Lamin A/C (a protein present in the nuclear lamina whose role is to protect the nuclear envelope from external stress and potential rupture) [ 31 , 32 , 33 , 34 , 35 , 36 ].…”

Study of Cell Migration under Mechanical Confinement in Microfluidic Lab-on-a-Chip

“…Beside the micrometric size of the constraints and the tailoring of their geometry, this approach allows for a high-resolution imaging of the migrating cells thanks to the thin and transparent device floor. This micro-constriction configuration has been used for more systematic biological studies like the adaptability of different cancer cell lines (MCF-10, MDA-MB-231) to micro-constrained environments and to study different migration behaviours depending on cancer cell invasiveness [20,21].…”

“…Once they reach the bloodstream, cells may experience confinement as they navigate through vessels of 3 − 4µm diameter [12,13]. Such confined migration induces significant structural changes in the cell's cytoskeleton [20,21] and focal adhesions, while also affecting nuclear shape and the distribution of Lamin A/C (a protein present in the nuclear lamina whose role is to protect the nuclear envelope from external stress and potential rupture) [22][23][24][25][26][27] .…”