9th Annual Symposium
Physics of Cancer
Leipzig, Germany
September 24-26, 2018
Contributed Talk
Loss of vimentin increases motility and nuclear damage in confined spaces
Alison Patteson1,2, Katarzyna Pogoda3, Paul Janmey1
1Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, USA
2Department of Physics, Syracuse University, 229C Physics Building, Syracuse, USA
3Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342 Krakow, Poland
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The migration of cells through tight constricting spaces or along fibrous tracks in tissues is important for biological processes, such as embryogenesis, wound healing, and cancer metastasis, and depends on the mechanical properties of the cytoskeleton. Migratory cells often express and upregulate the intermediate filament protein vimentin. The viscoelasticity of vimentin networks in shear deformation has been documented, but its role in motility is largely unexplored. We studied the effects of vimentin on cell motility and nuclear damage using mouse embryo fibroblasts derived from wild-type and vimentin-null mice. We find that loss of vimentin increases motility in confining environments, such as micro-fluidic channels and collagen matrices, that mimic interstitial spaces in tissues. Loss of vimentin leads to accumulated nuclear damage, in the form of blebs, nuclear envelope rupture, and enhanced DNA damage, which accompanies the migration of cells through small pores. Atomic force microscopy measurements reveal that the presence of vimentin enhances the perinuclear stiffness of the cell, to an extent that depends on surface ligand presentation and therefore signaling from extracellular matrix receptors. Together, our findings indicate that vimentin hinders three-dimensional motility by providing mechanical resistance against large strains and thereby protects the structural integrity of the cell and the nucleus. Reference: https://doi.org/10.1101/371047
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