6th Annual Symposium
Physics of Cancer
September 7-9, 2015
|PoC - Physics of Cancer - Annual Symposium|
Actin waves as determinants of circular cell trajectories in cell amoeboid migration
Department of Physics, Saarland University, Saarbrücken, Germany
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In the living body, migrating leukocytes have to squeeze in between neighboring cells, to overcome obstacles and to find their way in a very crowded environment. Leukocytes, such as dendritic cells (DCs), adapted to these constrains and use them specifically on their way of migrating in a confined environment. This type of migration is independent of integrins, much faster than integrin dependent migration and generally referred to as amoeboid migration. We carried out migration experiments with DCs confined in two-dimensions by adding a roof on top of the cells. We recorded cellular migration profiles by time-lapse fluorescent microscopy and evaluated single cell trajectories in terms of mean speed, persistence, path length and mean square displacement. Surprisingly, the analysis of the DC trajectories revealed curves with a preferred radius within one cell population. In a higher magnification and using TIRFM, we were further able to observe actin waves within these cells. We compared our experimental trajectories with trajectories generated from a theoretical model which uses actin polymerisation in cells independent of adhesion . In this model, the actin polymerisation generates actin waves within the cells which then generates - similar to our experimental data - curved segments in simulated cellular trajectories. We hypothesize that those actin waves determine the curvature of cellular trajectories during amoeboid migration.
We further investigated the relationship between cellular velocity and the preferred radius of cells and found a strong relation, both in the experimental and the theoretical dataset. The faster the cells, the larger the circles they migrate. In the theoretical model, actin waves occur spontaneously in the presence of a nucleation factor and independent of molecular motors such as myosin II. To verify these settings in our experimental setup we treated cells with the ROCK inhibitor Y27632, with the formin inhibitor SMIFH2, and with the Arp2/3 inhibitor Ck666. Our experimental data suggest that molecular motors, like myosin II may be indeed dispensable for the generation of cytoskeletal actin waves and the circular trajectories. However, formin inhibition completely annihilate waves formation. These results suggest that actin waves are like a steering wheel inside the cells generating circular trajectories and that we can use this actin-wave model in order to describe such curved migration in amoeboid cells.