Tue, 10/11/2015 - 14:15
,
Campus Saarbr├╝cken, Geb. E2 6, Raum E.04

Dr. Annica Gad
(
Host: Jun.-Prof. Dr. Franziska Lautenschl├Ąger
)
Department of Microbiology, Tumor, and Cell Biology, Karolinska Institute, Stockholm, Schweden

Cellular contractile forces and stiffness: nanoscale organization of vimentin, adhesions and HDAC6

To clarify the basis of cell migration, we analysed the contractile forces and nanoscale adhesions in fibroblast cells expressing constitutively active variants of Rho GTPases. While active RhoA induced large increases in the forces of cells, active Rac1 induced more moderate forces. RhoA caused reduced, and Rac1 an increased cell spreading areas. Both activities resulted in loss of thick stress fibres and focal adhesions, and in a more homogenous distribution of nanoscale adhesions. RhoA activity was found to increase the density of these adhesions. Our data suggest a Rac1-specific mode for cells to generate contractile forces, and that an increased density and more homogenous distribution of nanoscale adhesions are linked to increased cell forces.
We further found that oncogenes induced an increased density and homogenous distribution of nanoscale adhesions in cells, and a reduced parallel arrangement and increased width of vimentin intermediate filament fibres. We could further observe that oncogene expression increased the cell stiffness. Oncogenes also induced cell invasion and the levels of HDAC6, which was found to be required for the increased stiffness of oncogene-expressing cells. Taken together, our data suggest that oncogenes can increase cellular stiffness via an HDAC6-induced reorganization of the vimentin intermediate filament network.

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