6th Annual Symposium
Physics of Cancer
September 7-9, 2015
|PoC - Physics of Cancer - Annual Symposium|
Actomyosin network contractility triggers a stochastic transformation into highly motile amoeboid cells
Cell migration is key for various biological processes such as large-scale morphogenetic movements during embryonic development, proper immune responses or wound healing and potentially leads to cancer dissemination if reactivated by tumor cells. Using early zebrafish embryos from blastula to gastrula stages as a model system we investigated the emergence of migratory competence in embryonic progenitor cells. Based on a new set of experimental assays we were able to monitor cell transformations under defined culture conditions and within the physiological tissue environment. This experimental framework allowed us to uncover a simple polarization mechanism that drives the transformation of embryonic cells into a highly efficient amoeboid migration mode irrespective of the specific progenitor cell type . The observed amoeboid motility switch strongly depends on mechanical and contractile properties of the cellular cytoskeleton and was triggered by stochastic changes in cortex architecture when cells were exposed to biochemical stimuli or compressive forces from the 3D environment. Supported by theoretical modeling we show that transformation of cells is induced by cortical instabilities above a critical threshold level of Myosin II mediated contractility, resulting in polarized cells with exceptionally high retrograde cortical flows and a pronounced increase in cortical actomyosin density towards the cell rear. We further show through a combination of experiments and theory that these cortical flows are essential for stabilization of cell polarity and cell shape and, in addition, provide the intracellular force required for cell locomotion in confined environments. Finally, we provide evidence for the existence of a similar amoeboid migration phenotype within the gastrulating embryo in-vivo and show that amoeboid cell transformations can be induced in response to embryo wounding.