10th Annual Symposium
Physics of Cancer
September 25-27, 2019
|PoC - Physics of Cancer - Annual Symposium|
Vimentin provides the mechanical resilience required for amoeboid migration and protection of the nucleus
Saarland University, Physics Dept., Biophysics, 66123 Saarbrücken, Germany
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The innate immune response depends upon the transmigration of dendritic cells to the lymph nodes. These cells migrate through constricted passages in the tissue in an amoeboid mode of migration. As bidirectional interplay between vimentin intermediate filaments and actomyosin-dependent contractile elements has been shown to regulate adhesion-dependent migration, we examined whether this type of interactions could be involved also in amoeboid migration. To this end, we analyzed the motility and mechanical properties of dendritic cells in the presence and absence of vimentin. Vimentin-deficient dendritic cells were impaired in their capacity to perform amoeboid migration in confined environments. Importantly, these results could also be recapitulated in in vivo mouse experiments. Amoeboid migration requires optimal mechanical resilience of the dendritic cells to be successful. We therefore analyzed mechanical properties of immune cells by shear flow-induced mechanical deformation and AFM and observed that vimentin was required for both long- and short-term stiffness of amoeboid dendritic cells. When the differential involvement of the two cytoskeletal systems was analyzed, we observed that it is not the vimentin IFs per se that provide the required stiffness for dendritic cells but the interaction between vimentin IFs and actin. Furthermore, loss of vimentin resulted in a significant increase in DNA double strand breakage and cell death in dendritic cells subjected to migratory compression. These findings demonstrate that vimentin controls the mechanical properties required for dendritic cell migration and supports the mechanical protection of genome integrity during nuclear positioning and compression in migrating dendritic cells.