TY - JOUR A1 - Bae, Albert J. A1 - Beta, Carsten A1 - Bodenschatz, Eberhard T1 - Rapid switching of chemical signals in microfluidic devices N2 - We present an analysis of concentration switching times in microfluidic devices. The limits of rapid switching are analyzed based on the theory of dispersion by Taylor and Aris and compared to both experiments and numerical simulations. We focus on switching times obtained by photo-activation of caged compounds in a micro-flow (flow photolysis). The performance of flow photolysis is compared to other switching techniques. A flow chart is provided to facilitate the application of our theoretical analysis to microfluidic switching devices. Y1 - 2009 UR - http://pubs.rsc.org/en/Journals/JournalIssues/LC U6 - https://doi.org/10.1039/B905521e SN - 1473-0197 ER - TY - JOUR A1 - Amselem, Gabriel A1 - Theves, Matthias A1 - Bae, Albert J. A1 - Bodenschatz, Eberhard A1 - Beta, Carsten T1 - A stochastic description of dictyostelium chemotaxis JF - PLoS one N2 - Chemotaxis, the directed motion of a cell toward a chemical source, plays a key role in many essential biological processes. Here, we derive a statistical model that quantitatively describes the chemotactic motion of eukaryotic cells in a chemical gradient. Our model is based on observations of the chemotactic motion of the social ameba Dictyostelium discoideum, a model organism for eukaryotic chemotaxis. A large number of cell trajectories in stationary, linear chemoattractant gradients is measured, using microfluidic tools in combination with automated cell tracking. We describe the directional motion as the interplay between deterministic and stochastic contributions based on a Langevin equation. The functional form of this equation is directly extracted from experimental data by angle-resolved conditional averages. It contains quadratic deterministic damping and multiplicative noise. In the presence of an external gradient, the deterministic part shows a clear angular dependence that takes the form of a force pointing in gradient direction. With increasing gradient steepness, this force passes through a maximum that coincides with maxima in both speed and directionality of the cells. The stochastic part, on the other hand, does not depend on the orientation of the directional cue and remains independent of the gradient magnitude. Numerical simulations of our probabilistic model yield quantitative agreement with the experimental distribution functions. Thus our model captures well the dynamics of chemotactic cells and can serve to quantify differences and similarities of different chemotactic eukaryotes. Finally, on the basis of our model, we can characterize the heterogeneity within a population of chemotactic cells. Y1 - 2012 U6 - https://doi.org/10.1371/journal.pone.0037213 SN - 1932-6203 VL - 7 IS - 5 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Amselem, Gabriel A1 - Theves, Matthias A1 - Bae, Albert J. A1 - Beta, Carsten A1 - Bodenschatz, Eberhard T1 - Control parameter description of eukaryotic chemotaxis JF - Physical review letters N2 - The chemotaxis of eukaryotic cells depends both on the average concentration of the chemoattractant and on the steepness of its gradient. For the social amoeba Dictyostelium discoideum, we test quantitatively the prediction by Ueda and Shibata [Biophys. J. 93, 11 (2007)] that the efficacy of chemotaxis depends on a single control parameter only, namely, the signal-to-noise ratio (SNR), determined by the stochastic fluctuations of (i) the binding of the chemoattractant molecule to the transmembrane receptor and (ii) the intracellular activation of the effector of the signaling cascade. For SNR less than or similar to 1, the theory captures the experimental findings well, while for larger SNR noise sources further downstream in the signaling pathway need to be taken into account. Y1 - 2012 U6 - https://doi.org/10.1103/PhysRevLett.109.108103 SN - 0031-9007 VL - 109 IS - 10 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Westendorf, Christian A1 - Negrete, Jose A1 - Bae, Albert J. A1 - Sandmann, Rabea A1 - Bodenschatz, Eberhard A1 - Beta, Carsten T1 - Actin cytoskeleton of chemotactic amoebae operates close to the onset of oscillations JF - Proceedings of the National Academy of Sciences of the United States of America N2 - The rapid reorganization of the actin cytoskeleton in response to external stimuli is an essential property of many motile eukaryotic cells. Here, we report evidence that the actin machinery of chemotactic Dictyostelium cells operates close to an oscillatory instability. When averaging the actin response of many cells to a short pulse of the chemoattractant cAMP, we observed a transient accumulation of cortical actin reminiscent of a damped oscillation. At the single-cell level, however, the response dynamics ranged from short, strongly damped responses to slowly decaying, weakly damped oscillations. Furthermore, in a small subpopulation, we observed self-sustained oscillations in the cortical F-actin concentration. To substantiate that an oscillatory mechanism governs the actin dynamics in these cells, we systematically exposed a large number of cells to periodic pulse trains of different frequencies. Our results indicate a resonance peak at a stimulation period of around 20 s. We propose a delayed feedback model that explains our experimental findings based on a time-delay in the regulatory network of the actin system. To test the model, we performed stimulation experiments with cells that express GFP-tagged fusion proteins of Coronin and actin-interacting protein 1, as well as knockout mutants that lack Coronin and actin-interacting protein 1. These actin-binding proteins enhance the disassembly of actin filaments and thus allow us to estimate the delay time in the regulatory feedback loop. Based on this independent estimate, our model predicts an intrinsic period of 20 s, which agrees with the resonance observed in our periodic stimulation experiments. KW - Dictyostelium discoideum KW - microfluidics KW - caged cAMP KW - delay-differential equation Y1 - 2013 U6 - https://doi.org/10.1073/pnas.1216629110 SN - 0027-8424 VL - 110 IS - 10 SP - 3853 EP - 3858 PB - National Acad. of Sciences CY - Washington ER -