Scale-Free Chaos in the 2D Harmonically Confined Vicsek Model.

Animal motion and flocking are ubiquitous nonequilibrium phenomena that are often studied within active matter. In examples such as insect swarms, macroscopic quantities exhibit power laws with measurable critical exponents and ideas from phase transitions and statistical mechanics have been explored to explain them. The widely used Vicsek model with periodic boundary conditions has an ordering phase transition but the corresponding homogeneous ordered or disordered phases are different from observations of natural swarms. If a harmonic potential (instead of a periodic box) is used to confine particles, then the numerical simulations of the Vicsek model display periodic, quasiperiodic, and chaotic attractors. The latter are scale-free on critical curves that produce power laws and critical exponents. Here, we investigate the scale-free chaos phase transition in two space dimensions. We show that the shape of the chaotic swarm on the critical curve reflects the split between the core and the vapor of insects observed in midge swarms and that the dynamic correlation function collapses only for a finite interval of small scaled times. We explain the algorithms used to calculate the largest Lyapunov exponents, the static and dynamic critical exponents, and compare them to those of the three-dimensional model.

Coarse-graining the vertex model and its response to shear.

Tissue dynamics and collective cell motion are crucial biological processes. Their biological machinery is mostly known, and simulation models such as the active vertex model exist and yield reasonable agreement with experimental observations such as tissue fluidization or fingering. However, a good and well-founded continuum description for tissues remains to be developed. In this work, we derive a macroscopic description for a two-dimensional cell monolayer by coarse-graining the vertex model through the Poisson bracket approach. We obtain equations for cell density, velocity, and the cellular shape tensor. We then study the homogeneous steady states, their stability (which coincides with thermodynamic stability), and especially their behavior under an externally applied shear. Our results contribute to elucidate the interplay between flow and cellular shape. The obtained macroscopic equations present a good starting point for adding cell motion, morphogenetic, and other biologically relevant processes.

Hyperchaos, Intermittency, Noise and Disorder in Modified Semiconductor Superlattices.

Weakly coupled semiconductor superlattices under DC voltage bias are nonlinear systems with many degrees of freedom whose nonlinearity is due to sequential tunneling of electrons. They may exhibit spontaneous chaos at room temperature and act as fast physical random number generator devices. Here we present a general sequential transport model with different voltage drops at quantum wells and barriers that includes noise and fluctuations due to the superlattice epitaxial growth. Excitability and oscillations of the current in superlattices with identical periods are due to nucleation and motion of charge dipole waves that form at the emitter contact when the current drops below a critical value. Insertion of wider wells increases superlattice excitability by allowing wave nucleation at the modified wells and more complex dynamics. Then hyperchaos and different types of intermittent chaos are possible on extended DC voltage ranges. Intrinsic shot and thermal noises and external noises produce minor effects on chaotic attractors. However, random disorder due to growth fluctuations may suppress any regular or chaotic current oscillations. Numerical simulations show that more than 70% of samples remain chaotic when the standard deviation of their fluctuations due to epitaxial growth is below 0.024 nm (10% of a single monolayer) whereas for 0.015 nm disorder suppresses chaos.

Kovacs Memory Effect with an Optically Levitated Nanoparticle.

The understanding of the dynamics of nonequilibrium cooling and heating processes at the nanoscale is still an open problem. These processes can follow surprising relaxation paths due to, e.g., memory effects, which significantly alter the expected equilibration routes. The Kovacs effect can take place when a thermalization process is suddenly interrupted by a change of the bath temperature, leading to a nonmonotonic evolution of the energy of the system. Here, we demonstrate that the Kovacs effect can be observed in the thermalization of the center of mass motion of a levitated nanoparticle. The temperature is controlled during the experiment through an external source of white Gaussian noise that mimics an effective thermal bath at a temperature that can be changed faster than any relaxation time of the system. We describe our experiments in terms of the dynamics of a Brownian particle in a harmonic trap without any fitting parameter, suggesting that the Kovacs effect can appear in a large variety of systems.

Fingering instability in spreading epithelial monolayers: roles of cell polarisation, substrate friction and contractile stresses.

Collective cell migration plays a crucial role in many developmental processes that underlie morphogenesis, wound healing, or cancer progression. In such coordinated behaviours, cells are organised in coherent structures and actively migrate to serve different biological purposes. In some contexts, namely during epithelial wound healing, it is well known that a migrating free-edge monolayer develops finger-like instabilities, yet the onset is still under debate. Here, by means of theory and numerical simulations, we shed light on the main mechanisms driving the instability process, analysing the linear and nonlinear dynamics of a continuum compressible polar fluid. In particular, we assess the role of cell polarisation, substrate friction, and contractile stresses. Linear theory shows that it is crucial to analyse the perturbation transient dynamics, since we unravel a plethora of crossovers between different exponential growth rates during the linear regime. Numerical simulations suggest that cell-substrate friction could be the mechanism responsible for the formation of complex finger-like structures at the edge, since it triggers secondary fingering instabilities and tip-splitting phenomena. Finally, we obtain a critical contractile stress that depends on cell-substrate friction and the initial-to-nematic length ratio, characterising an active wetting-dewetting transition. In the dewetting scenario, the monolayer retracts and becomes stable without developing finger-like structures.

Anomalous Angiogenesis in Retina.

Age-related macular degeneration (AMD) may cause severe loss of vision or blindness, particularly in elderly people. Exudative AMD is characterized by the angiogenesis of blood vessels growing from underneath the macula, crossing the blood-retina barrier (which comprises Bruch's membrane (BM) and the retinal pigmentation epithelium (RPE)), leaking blood and fluid into the retina and knocking off photoreceptors. Here, we simulate a computational model of angiogenesis from the choroid blood vessels via a cellular Potts model, as well as BM, RPE cells, drusen deposits and photoreceptors. Our results indicate that improving AMD may require fixing the impaired lateral adhesion between RPE cells and with BM, as well as diminishing Vessel Endothelial Growth Factor (VEGF) and Jagged proteins that affect the Notch signaling pathway. Our numerical simulations suggest that anti-VEGF and anti-Jagged therapies could temporarily halt exudative AMD while addressing impaired cellular adhesion, which could be more effective over a longer time-span.

Tracking collective cell motion by topological data analysis.

By modifying and calibrating an active vertex model to experiments, we have simulated numerically a confluent cellular monolayer spreading on an empty space and the collision of two monolayers of different cells in an antagonistic migration assay. Cells are subject to inertial forces and to active forces that try to align their velocities with those of neighboring ones. In agreement with experiments in the literature, the spreading test exhibits formation of fingers in the moving interfaces, there appear swirls in the velocity field, and the polar order parameter and the correlation and swirl lengths increase with time. Numerical simulations show that cells inside the tissue have smaller area than those at the interface, which has been observed in recent experiments. In the antagonistic migration assay, a population of fluidlike Ras cells invades a population of wild type solidlike cells having shape parameters above and below the geometric critical value, respectively. Cell mixing or segregation depends on the junction tensions between different cells. We reproduce the experimentally observed antagonistic migration assays by assuming that a fraction of cells favor mixing, the others segregation, and that these cells are randomly distributed in space. To characterize and compare the structure of interfaces between cell types or of interfaces of spreading cellular monolayers in an automatic manner, we apply topological data analysis to experimental data and to results of our numerical simulations. We use time series of data generated by numerical simulations to automatically group, track and classify the advancing interfaces of cellular aggregates by means of bottleneck or Wasserstein distances of persistent homologies. These techniques of topological data analysis are scalable and could be used in studies involving large amounts of data. Besides applications to wound healing and metastatic cancer, these studies are relevant for tissue engineering, biological effects of materials, tissue and organ regeneration.

Notch signaling and taxis mechanisms regulate early stage angiogenesis: A mathematical and computational model.

During angiogenesis, new blood vessels sprout and grow from existing ones. This process plays a crucial role in organ development and repair, in wound healing and in numerous pathological processes such as cancer progression or diabetes. Here, we present a mathematical model of early stage angiogenesis that permits exploration of the relative importance of mechanical, chemical and cellular cues. Endothelial cells proliferate and move over an extracellular matrix by following external gradients of Vessel Endothelial Growth Factor, adhesion and stiffness, which are incorporated to a Cellular Potts model with a finite element description of elasticity. The dynamics of Notch signaling involving Delta-4 and Jagged-1 ligands determines tip cell selection and vessel branching. Through their production rates, competing Jagged-Notch and Delta-Notch dynamics determine the influence of lateral inhibition and lateral induction on the selection of cellular phenotypes, branching of blood vessels, anastomosis (fusion of blood vessels) and angiogenesis velocity. Anastomosis may be favored or impeded depending on the mechanical configuration of strain vectors in the ECM near tip cells. Numerical simulations demonstrate that increasing Jagged production results in pathological vasculatures with thinner and more abundant vessels, which can be compensated by augmenting the production of Delta ligands.

Fast Detection of a Weak Signal by a Stochastic Resonance Induced by a Coherence Resonance in an Excitable GaAs/Al_{0.45}Ga_{0.55}As Superlattice.

The effect of a coherence resonance is observed experimentally in a GaAs/Al_{0.45}Ga_{0.55}As superlattice under dc bias at room temperature, which is driven by noise. For an applied voltage, for which no current self-oscillations are observed, regular current self-oscillations with a frequency of about 82 MHz are induced by exceeding a certain noise amplitude. In addition, a novel kind of a stochastic resonance is identified, which is triggered by the coherence resonance. This stochastic resonance appears when the device is driven by an external ac signal with a frequency, which is relatively close to that of the regular current self-oscillations at the coherence resonance. The intrinsic oscillation mode in the coherence resonance is found to be phase locked by an extremely weak ac signal. It is demonstrated that an excitable superlattice device can be used for the fast detection of weak signals submerged in noise. These results are very well reproduced by results using numerical simulations based on a sequential resonant tunneling model of nonlinear electron transport in semiconductor superlattices.

Coherence Resonance and Stochastic Resonance in an Excitable Semiconductor Superlattice.

Collective electron transport causes a weakly coupled semiconductor superlattice under dc voltage bias to be an excitable system with 2N+2 degrees of freedom: electron densities and fields at N superlattice periods plus the total current and the field at the injector. External noise of sufficient amplitude induces regular current self-oscillations (coherence resonance) in states that are stationary in the absence of noise. Numerical simulations show that these oscillations are due to the repeated nucleation and motion of charge dipole waves that form at the emitter when the current falls below a critical value. At the critical current, the well-to-well tunneling current intersects the contact load line. We have determined the device-dependent critical current for the coherence resonance from experiments and numerical simulations. We have also described through numerical simulations how a coherence resonance triggers a stochastic resonance when its oscillation mode becomes locked to a weak ac external voltage signal. Our results agree with the experimental observations.

Parameter dependence of high-frequency nonlinear oscillations and intrinsic chaos in short GaAs/(Al, Ga)As superlattices.

We explore the design parameter space of short (5-25 period), n-doped, Ga/(Al,Ga)As semiconductor superlattices (SSLs) in the sequential resonant tunneling regime. We consider SSLs at cool (77 K) and warm (295 K) temperatures, simulating the electronic response to variations in (a) the number of SSL periods, (b) the contact conductivity, and (c) the strength of disorder (aperiodicities). Our analysis shows that the chaotic dynamical phases exist on a number of sub-manifolds of codimension zero within the design parameter space. This result provides an encouraging guide towards the experimental observation of high-frequency intrinsic dynamical chaos in shorter SSLs.

Noise-enhanced chaos in a weakly coupled GaAs/(Al,Ga)As superlattice.

Noise-enhanced chaos in a doped, weakly coupled GaAs/Al_{0.45}Ga_{0.55}As superlattice has been observed at room temperature in experiments as well as in the results of the simulation of nonlinear transport based on a discrete tunneling model. When external noise is added, both the measured and simulated current-versus-time traces contain irregularly spaced spikes for particular applied voltages, which separate a regime of periodic current oscillations from a region of no current oscillations at all. In the voltage region without current oscillations, the electric-field profile consist of a low-field domain near the emitter contact separated by a domain wall consisting of a charge accumulation layer from a high-field regime closer to the collector contact. With increasing noise amplitude, spontaneous chaotic current oscillations appear over a wider bias voltage range. For these bias voltages, the domain boundary between the two electric-field domains becomes unstable and very small current or voltage fluctuations can trigger the domain boundary to move toward the collector and induce chaotic current spikes. The experimentally observed features are qualitatively very well reproduced by the simulations. Increased noise can consequently enhance chaotic current oscillations in semiconductor superlattices.

On the mathematical modelling of tumor-induced angiogenesis.

An angiogenic system is taken as an example of extremely complex ones in the field of Life Sciences, from both analytical and computational points of view, due to the strong coupling between the kinetic parameters of the relevant branching - growth - anastomosis stochastic processes of the capillary network, at the microscale, and the family of interacting underlying biochemical fields, at the macroscale. To reduce this complexity, for a conceptual stochastic model we have explored how to take advantage of the system intrinsic multiscale structure: one might describe the stochastic dynamics of the cells at the vessel tip at their natural microscale, whereas the dynamics of the underlying fields is given by a deterministic mean field approximation obtained by an averaging at a suitable mesoscale. But the outcomes of relevant numerical simulations show that the proposed model, in presence of anastomosis, is not self-averaging, so that the ``propagation of chaos" assumption cannot be applied to obtain a deterministic mean field approximation. On the other hand we have shown that ensemble averages over many realizations of the stochastic system may better correspond to a deterministic reaction-diffusion system.