7th Annual Symposium
Physics of Cancer
October 4-6, 2016
|PoC - Physics of Cancer - Annual Symposium|
Dynamics of circular dorsal ruffles and their role in cancer
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Cells utilize the actin cytoskeleton to actively remodel their morphologies. This enables them to internalize extracellular fluid and activated membrane receptors via macropinocytosis. To form large vesicles this endocytotic mechanism relies on the contraction and closure of actin-based, ring-shaped vertical protrusions at the dorsal cell membrane that are known as Circular Dorsal Ruffles (CDRs). CDRs are essential to a range of vital and pathogenic processes alike. For cancer cells CDRs seem to play two oppositional roles: Loss of CDRs is associated with failure of the shut down of signalling by activated growth factor receptors, which leads to uncontrolled cell growth. On the other hand CDRs also serve the dissociation of the cytoskeleton, which facilitates the ability of cancer cells for mesenchymal migration.
Despite much scientific attention, the mechanism of how proteins self-organize to form these dynamic ring-shaped structures remains unknown. We show that CDRs are propagating fronts of actin polymerization in a bistable system. A new model assigns the expansion and contraction of waves to distinct counter-propagating fronts of different velocities. Under a change in biochemical conditions, CDR may be pinned and fluctuate near the cell boundary or result in complex spiral wave dynamics due to a wave instability. Indeed, both phenomena are found in our data  pointing at the conditions for which macropinocytosis is suppressed. The latter scenario is valid for, e.g., confined CDRs on quasi one-dimensional tracks. We investigate the stochastic dynamics of these states as a function of biochemical conditions and find evidence of stochastic resonance.