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Rho-GTPases are master regulators of polarity establishment and cell morphology. Positive feedback enables concentration of Rho-GTPases into clusters at the cell cortex, from where they regulate the cytoskeleton. Different cell types reproducibly generate either one (e.g. the front of a migrating cell) or several clusters (e.g. the multiple dendrites of a neuron), but the mechanistic basis for unipolar or multipolar outcomes is unclear. The design principles of Rho-GTPase circuits are captured by two-component reaction-diffusion models based on conserved aspects of Rho-GTPase biochemistry. Some such models display rapid winner-takes-all competition between clusters, yielding a unipolar outcome. Other models allow prolonged co-existence of clusters. We investigate the behavior of a simple class of models and show that while the timescale of competition varies enormously depending on model parameters, a single factor explains a large majority of this variation. The dominant factor concerns the degree to which the maximal active GTPase concentration in a cluster approaches a "saturation point" determined by model parameters. We suggest that both saturation and the effect of saturation on competition reflect fundamental properties of the Rho-GTPase polarity machinery, regardless of the specific feedback mechanism, which predict whether the system will generate unipolar or multipolar outcomes.
Assuntos
Polaridade Celular/fisiologia , Modelos Biológicos , Proteínas rho de Ligação ao GTP/metabolismo , Ligação Competitiva , Biologia Computacional , Simulação por Computador , Citoplasma/metabolismo , Citoesqueleto/metabolismo , Cinética , Agregados Proteicos , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas rho de Ligação ao GTP/químicaRESUMO
The neurotransmitter dopamine (DA) is known to be influenced by the circadian timekeeping system in the mammalian brain. We have previously created a single-cell differential equations model to understand the mechanisms behind circadian rhythms of extracellular DA. In this paper, we investigate the dynamics in our model and study different behaviors such as entrainment to the 24-hour light-dark cycle and robust periodicity versus decoupling, quasiperiodicity, and chaos. Imbalances in DA are often accompanied by disrupted circadian rhythms, such as in Parkinson's disease, hyperactivity, and mood disorders. Our model provides new insights into the links between the circadian clock and DA. We show that the daily rhythmicity of DA can be disrupted by decoupling between interlocked loops of the clock circuitry or by quasiperiodic clock behaviors caused by misalignment with the light-dark cycle. The model can be used to further study how the circadian clock affects the dopaminergic system, and to help develop therapeutic strategies for disrupted DA rhythms.
Assuntos
Relógios Circadianos , Doença de Parkinson , Animais , Ritmo Circadiano , Dopamina , Mamíferos , FotoperíodoRESUMO
Acoustics-based tweezers provide a unique toolset for contactless, label-free, and precise manipulation of bioparticles and bioanalytes. Most acoustic tweezers rely on acoustic radiation forces; however, the accompanying acoustic streaming often generates unpredictable effects due to its nonlinear nature and high sensitivity to the three-dimensional boundary conditions. Here, we demonstrate acoustohydrodynamic tweezers, which generate stable, symmetric pairs of vortices to create hydrodynamic traps for object manipulation. These stable vortices enable predictable control of a flow field, which translates into controlled motion of droplets or particles on the operating surface. We built a programmable droplet-handling platform to demonstrate the basic functions of planar-omnidirectional droplet transport, merging droplets, and in situ mixing via a sequential cascade of biochemical reactions. Our acoustohydrodynamic tweezers enables improved control of acoustic streaming and demonstrates a previously unidentified method for contact-free manipulation of bioanalytes and digitalized liquid handling based on a compact and scalable functional unit.
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This corrects the article DOI: 10.1103/PhysRevE.92.043016.
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The surface structure of converging thin fluid films displays self-similar behavior, as was shown in the work by Diez et al. [Q. Appl. Math. 210, 155 (1990)]. Extracting the related similarity scaling exponents from either numerical or experimental data is nontrivial. Here we provide two such methods. We apply them to experimental and numerical data on converging fluid films driven by both surface tension and gravitational forcing. In the limit of pure gravitational driving, we recover Diez' semianalytic result, but our methods also allow us to explore the entire regime of mixed capillary and gravitational driving, up to entirely surface-tension-driven flows. We find scaling forms of smoothly varying exponents up to surprisingly small Bond numbers. Our experimental results are in reasonable agreement with our numerical simulations, which confirm theoretically obtained relations between the scaling exponents.
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We present experimental and computational results indicating the existence of finite-amplitude fingering solutions in a flow of a thin film of a viscous fluid driven by thermally induced Marangoni stresses. Using carefully controlled experiments, spatially periodic perturbations to the contact line of an initially uniform thin film flow are shown to lead to the development of steady-profile two-dimensional traveling wave fingers. Using an infrared laser and scanning mirror, we impose thermal perturbations with a known wavelength to an initially uniform advancing fluid front. As the front advances in the experiment, we observe convergence to fingers with the initially prescribed wavelength. Experiments and numerical computations show that this family of solutions arises from a subcritical bifurcation.