Flussgetrieben cAMP-Wellen, phasengekoppelte Muster und Arnold-Zungen waehrend der Aggregation von Dictyostelium discoideum.
Zusammenfassung der Projektergebnisse
The first focus of my DFG project was on the influence of spatial heterogeneities on the collective behavior of signaling amoeboid cells. Our experimental observations show that aggregation of D. d. cells can be controlled using millimetersized pillars as centers of aggregation. In these experiments, a population of starved cells is placed on a PDMS substrate with periodic arrangement of pillars. These pillars have a diameter of 1 mm and are spaced 5 mm away from each other. Interestingly, in these experiments with caffeine treated cells, we observe concentric cAMP waves that initiate almost synchronously at the pillars and propagate outwards. These waves have a higher frequency than the other firing centers and dominate the system dynamics. The cells respond chemotactically to these circular waves and stream towards the pillars, forming periodic domains that reflect the periodicity of the underlying lattice. We compared these experiments with numerical simulations of a reaction-diffusion model to study the role of caffeine and characteristics of the boundary conditions given by the obstacles. These simulations show that a critical minimum accumulation of cAMP around the obstacles is required for the pillars to act as the wave source. This critical value depends on the cAMP production rate, a variable which we could experimentally decrease by adding caffeine. Moreover, our results show that caffeine reduces the excitability threshold of the cells and increases the sensitivity to cAMP accumulation around the obstacles. Without caffeine, non-treated cells are less sensitive to cAMP accumulation around the pillars and ignore them, as observed in the experiments. Our experiments and simulations suggest that in nature the excitability threshold of the cells is tuned by an adaptation process that optimizes the sensitivity to waves while ignoring the cAMP accumulations around spatial heterogeneities which can interrupt the development process of the cells. In the second part of the project, we focused on “Influence of Fast Advective Flows on Pattern Formation in Dictyostelium discoideum”, which are published in Plos One. In this work, we performed experiments on pattern formation of D. discoideum cells in a microfluidic channel (50mm× 2mm×100µm) under a constant buffer flow. The external flow advects the signaling molecule cAMP downstream, while the chemotactic cells attached to the glass substrate are not transported with the flow. At high flow velocities, elongated cAMP waves are formed that cover the whole length of the channel and propagate both parallel and perpendicular to the flow direction. While the wave period and transverse propagation velocity are constant, parallel wave velocity and the wave width increase linearly with the imposed flow. An interesting observation in these experiments was that the acquired wave shape is highly dependent on the wave generation site and the strength of the imposed flow. Wave shape and velocity in experiments was in good agreement with numerical simulations of a reaction-diffusion. These results play an important role in understanding the process of pattern formation and aggregation of D. discoideum cells in their natural habitat that are often exposed to fluid flows. In the last part, we performed flow experiments in a microfluidic set up focusing on the effect of upstream boundary conditions. Interestingly, we observed that flow can rescue PdsA- mutants that fail to aggregate in the absence of flow. These cells normally produce almost no Phosphodiestrase which is responsible for cAMP degradation. Furthermore, we observed boundary-driven waves upstream that fail to propagate through the channel at low flow velocities but as he increases the imposed flow velocity, the cAMP waves propagate through. Experiments with PdsA- cells were motivated by our numerical simulations predicting that a reaction-diffusionadvection model with a Dirichlet boundary condition imposed upstream shows an instability at low degradation rates of cAMP. This boundary-driven instability acts as a continuous wave source, creating a local periodic excitation near the boundary, which initiates waves travelling downstream.
Projektbezogene Publikationen (Auswahl)
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Convective instability and boundary driven oscillations in a reaction-diffusionadvection model. Chaos 27, 103110 (2017)
E. Vidal, V. Zykov, E. Bodenschatz, A. Gholami
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Influence of fast advective flows on pattern formation of Dictyostelium discoideum. Plos One 13(3): e0194859 (2018)
T. Eckstein, E. Vidal, A. Bae, V. Zykov, E. Bodenschatz, A. Gholami
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Influence of Flow and Spatial Heterogeneities on Pattern Formation of Dictyostelium discoideum, Georg August Universität, Göttingen, Germany (2019)
E. Vidal-Henriquez
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Spontaneous center formation in Dictyostelium discoideum. Scientific Reports (2019)
E. Vidal, A. Gholami
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Experimental observation of boundary-driven oscillations in a reaction-diffusionadvection system, Soft Matter (2020)
T. Eckstein, E. Vidal, A Gholami
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Perturbation of Pattern Formation in Dictyostelium Discoideum via Flow and Spatial Heterogeneities, Georg August Universität, Göttingen, Germany (2020)
T. Eckstein
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Spatial heterogeneities shape collective behavior of signaling amoeboid cells, Science Signaling 13, eaaz3975 (2020)
T. Eckstein, E. Vidal, A. Bae and A. Gholami
