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Sci Rep. 2017 Feb 16;7:42780. doi: 10.1038/srep42780.

Focal adhesion kinase activity is required for actomyosin contractility-based invasion of cells into dense 3D matrices.

Author information

1
Institute of Experimental Physics I, Biological Physics Division, Faculty of Physics and Earth Science, University of Leipzig, Leipzig, Germany.
2
Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.

Abstract

The focal adhesion kinase (FAK) regulates the dynamics of integrin-based cell adhesions important for motility. FAK's activity regulation is involved in stress-sensing and focal-adhesion turnover. The effect of FAK on 3D migration and cellular mechanics is unclear. We analyzed FAK knock-out mouse embryonic fibroblasts and cells expressing a kinase-dead FAK mutant, R454-FAK, in comparison to FAK wild-type cells. FAK knock-out and FAKR454/R454 cells invade dense 3D matrices less efficiently. These results are supported by FAK knock-down in wild-type fibroblasts and MDA-MB-231 human breast cancer cells showing reduced invasiveness. Pharmacological interventions indicate that in 3D matrices, cells deficient in FAK or kinase-activity behave similarly to wild-type cells treated with inhibitors of Src-activity or actomyosin-contractility. Using magnetic tweezers experiments, FAKR454/R454 cells are shown to be softer and exhibit impaired adhesion to fibronectin and collagen, which is consistent with their reduced 3D invasiveness. In line with this, FAKR454/R454 cells cannot contract the matrix in contrast to FAK wild-type cells. Finally, our findings demonstrate that active FAK facilitates 3D matrix invasion through increased cellular stiffness and transmission of actomyosin-dependent contractile force in dense 3D extracellular matrices.

PMID:
28202937
PMCID:
PMC5311912
DOI:
10.1038/srep42780
[Indexed for MEDLINE]
Free PMC Article

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