7th Annual Symposium
Physics of Cancer
Leipzig, Germany
October 4-6, 2016
Invited Talk
Dynamics of circular dorsal ruffles and their role in cancer
Erik Bernitt1,2,3, Julia Lange1, Malte Ohmstede1, Nir Gov2, Arik Yochelis3, Hans-Günther Döbereiner1
1Institut für Biophysik, Universität Bremen, 28359 Bremen, Germany
2Department of Chemical Physics, Weizmann Institute of Science, 76100 Rehovot, Israel
3Department of Solar Energy and Environmental Physics, Ben-Gurion University of the Negev, 849900 Midreshet Ben-Gurion, Israel
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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 [1] 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.
[1]E.Bernitt, C.G.Koh, N.Gov, HG DöbereinerDynamics of Actin Waves on Patterned Substrates: A Quantitative Analysis of Circular Dorsal Ruffles, PLOS One 10 (1), e0115857 (2015)
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