Microfluidic single-cell measurements of oxidative stress as a function of cell cycle position.

Single-cell measurements routinely demonstrate high levels of variation between cells, but fewer studies provide insight into the analytical and biological sources of this variation. This is particularly true of chemical cytometry, in which individual cells are lysed and their contents separated, compared to more established single-cell measurements of the genome and transcriptome. To characterize population-level variation and its sources, we analyzed oxidative stress levels in 1278 individual Dictyostelium discoideum cells as a function of exogenous stress level and cell cycle position. Cells were exposed to varying levels of oxidative stress via singlet oxygen generation using the photosensitizer Rose Bengal. Single-cell data reproduced the dose-response observed in ensemble measurements by CE-LIF, superimposed with high levels of heterogeneity. Through experiments and data analysis, we explored possible biological sources of this heterogeneity. No trend was observed between population variation and oxidative stress level, but cell cycle position was a major contributor to heterogeneity in oxidative stress. Cells synchronized to the same stage of cell division were less heterogeneous than unsynchronized cells (RSD of 37-51% vs 93%), and mitotic cells had higher levels of reactive oxygen species than interphase cells. While past research has proposed changes in cell size during the cell cycle as a source of biological noise, the measurements presented here use an internal standard to normalize for effects of cell volume, suggesting a more complex contribution of cell cycle to heterogeneity of oxidative stress.

Detecting disturbances in network-coupled dynamical systems with machine learning.

Identifying disturbances in network-coupled dynamical systems without knowledge of the disturbances or underlying dynamics is a problem with a wide range of applications. For example, one might want to know which nodes in the network are being disturbed and identify the type of disturbance. Here, we present a model-free method based on machine learning to identify such unknown disturbances based only on prior observations of the system when forced by a known training function. We find that this method is able to identify the locations and properties of many different types of unknown disturbances using a variety of known forcing functions. We illustrate our results with both linear and nonlinear disturbances using food web and neuronal activity models. Finally, we discuss how to scale our method to large networks.

Multistability in coupled oscillator systems with higher-order interactions and community structure.

We study synchronization dynamics in populations of coupled phase oscillators with higher-order interactions and community structure. We find that the combination of these two properties gives rise to a number of states unsupported by either higher-order interactions or community structure alone, including synchronized states with communities organized into clusters in-phase, anti-phase, and a novel skew-phase, as well as an incoherent-synchronized state. Moreover, the system displays strong multistability with many of these states stable at the same time. We demonstrate our findings by deriving the low dimensional dynamics of the system and examining the system's bifurcations using stability analysis and perturbation theory.

Synchronization of phase oscillators on complex hypergraphs.

We study the effect of structured higher-order interactions on the collective behavior of coupled phase oscillators. By combining a hypergraph generative model with dimensionality reduction techniques, we obtain a reduced system of differential equations for the system's order parameters. We illustrate our framework with the example of a hypergraph with hyperedges of sizes 2 (links) and 3 (triangles). For this case, we obtain a set of two coupled nonlinear algebraic equations for the order parameters. For strong values of coupling via triangles, the system exhibits bistability and explosive synchronization transitions. We find conditions that lead to bistability in terms of hypergraph properties and validate our predictions with numerical simulations. Our results provide a general framework to study the synchronization of phase oscillators in hypergraphs, and they can be extended to hypergraphs with hyperedges of arbitrary sizes, dynamic-structural correlations, and other features.

Tiered synchronization in coupled oscillator populations with interaction delays and higher-order interactions.

We study synchronization in large populations of coupled phase oscillators with time delays and higher-order interactions. With each of these effects individually giving rise to bistability between incoherence and synchronization via subcriticality at the onset of synchronization and the development of a saddle node, we find that their combination yields another mechanism behind bistability, where supercriticality at onset may be maintained; instead, the formation of two saddle nodes creates tiered synchronization, i.e., bistability between a weakly synchronized state and a strongly synchronized state. We demonstrate these findings by first deriving the low dimensional dynamics of the system and examining the system bifurcations using a stability and steady-state analysis.

Balanced Hodge Laplacians optimize consensus dynamics over simplicial complexes.

Despite the vast literature on network dynamics, we still lack basic insights into dynamics on higher-order structures (e.g., edges, triangles, and more generally, k-dimensional "simplices") and how they are influenced through higher-order interactions. A prime example lies in neuroscience where groups of neurons (not individual ones) may provide building blocks for neurocomputation. Here, we study consensus dynamics on edges in simplicial complexes using a type of Laplacian matrix called a Hodge Laplacian, which we generalize to allow higher- and lower-order interactions to have different strengths. Using techniques from algebraic topology, we study how collective dynamics converge to a low-dimensional subspace that corresponds to the homology space of the simplicial complex. We use the Hodge decomposition to show that higher- and lower-order interactions can be optimally balanced to maximally accelerate convergence and that this optimum coincides with a balancing of dynamics on the curl and gradient subspaces. We additionally explore the effects of network topology, finding that consensus over edges is accelerated when two-simplices are well dispersed, as opposed to clustered together.

Geometric unfolding of synchronization dynamics on networks.

We study the synchronized state in a population of network-coupled, heterogeneous oscillators. In particular, we show that the steady-state solution of the linearized dynamics may be written as a geometric series whose subsequent terms represent different spatial scales of the network. Specifically, each additional term incorporates contributions from wider network neighborhoods. We prove that this geometric expansion converges for arbitrary frequency distributions and for both undirected and directed networks provided that the adjacency matrix is primitive. We also show that the error in the truncated series grows geometrically with the second largest eigenvalue of the normalized adjacency matrix, analogously to the rate of convergence to the stationary distribution of a random walk. Last, we derive a local approximation for the synchronized state by truncating the spatial series, at the first neighborhood term, to illustrate the practical advantages of our approach.

Abrupt Desynchronization and Extensive Multistability in Globally Coupled Oscillator Simplexes.

Collective behavior in large ensembles of dynamical units with nonpairwise interactions may play an important role in several systems ranging from brain function to social networks. Despite recent work pointing to simplicial structure, i.e., higher-order interactions between three or more units at a time, their dynamical characteristics remain poorly understood. Here we present an analysis of the collective dynamics of such a simplicial system, namely coupled phase oscillators with three-way interactions. The simplicial structure gives rise to a number of novel phenomena, most notably a continuum of abrupt desynchronization transitions with no abrupt synchronization transition counterpart, as well as extensive multistability whereby infinitely many stable partially synchronized states exist. Our analysis sheds light on the complexity that can arise in physical systems with simplicial interactions like the human brain and the role that simplicial interactions play in storing information.

Collective Phenomena Emerging from the Interactions between Dynamical Processes in Multiplex Networks.

We introduce a framework to intertwine dynamical processes of different nature, each with its own distinct network topology, using a multilayer network approach. As an example of collective phenomena emerging from the interactions of multiple dynamical processes, we study a model where neural dynamics and nutrient transport are bidirectionally coupled in such a way that the allocation of the transport process at one layer depends on the degree of synchronization at the other layer, and vice versa. We show numerically, and we prove analytically, that the multilayer coupling induces a spontaneous explosive synchronization and a heterogeneous distribution of allocations, otherwise not present in the two systems considered separately. Our framework can find application to other cases where two or more dynamical processes such as synchronization, opinion formation, information diffusion, or disease spreading, are interacting with each other.

Uncovering low dimensional macroscopic chaotic dynamics of large finite size complex systems.

In the last decade, it has been shown that a large class of phase oscillator models admit low dimensional descriptions for the macroscopic system dynamics in the limit of an infinite number N of oscillators. The question of whether the macroscopic dynamics of other similar systems also have a low dimensional description in the infinite N limit has, however, remained elusive. In this paper, we show how techniques originally designed to analyze noisy experimental chaotic time series can be used to identify effective low dimensional macroscopic descriptions from simulations with a finite number of elements. We illustrate and verify the effectiveness of our approach by applying it to the dynamics of an ensemble of globally coupled Landau-Stuart oscillators for which we demonstrate low dimensional macroscopic chaotic behavior with an effective 4-dimensional description. By using this description, we show that one can calculate dynamical invariants such as Lyapunov exponents and attractor dimensions. One could also use the reconstruction to generate short-term predictions of the macroscopic dynamics.

On controlling networks of limit-cycle oscillators.

The control of network-coupled nonlinear dynamical systems is an active area of research in the nonlinear science community. Coupled oscillator networks represent a particularly important family of nonlinear systems, with applications ranging from the power grid to cardiac excitation. Here, we study the control of network-coupled limit cycle oscillators, extending the previous work that focused on phase oscillators. Based on stabilizing a target fixed point, our method aims to attain complete frequency synchronization, i.e., consensus, by applying control to as few oscillators as possible. We develop two types of controls. The first type directs oscillators towards larger amplitudes, while the second does not. We present numerical examples of both control types and comment on the potential failures of the method.

Optimal synchronization of directed complex networks.

We study optimal synchronization of networks of coupled phase oscillators. We extend previous theory for optimizing the synchronization properties of undirected networks to the important case of directed networks. We derive a generalized synchrony alignment function that encodes the interplay between the network structure and the oscillators' natural frequencies and serves as an objective measure for the network's degree of synchronization. Using the generalized synchrony alignment function, we show that a network's synchronization properties can be systematically optimized. This framework also allows us to study the properties of synchrony-optimized networks, and in particular, investigate the role of directed network properties such as nodal in- and out-degrees. For instance, we find that in optimally rewired networks, the heterogeneity of the in-degree distribution roughly matches the heterogeneity of the natural frequency distribution, but no such relationship emerges for out-degrees. We also observe that a network's synchronization properties are promoted by a strong correlation between the nodal in-degrees and the natural frequencies of oscillators, whereas the relationship between the nodal out-degrees and the natural frequencies has comparatively little effect. This result is supported by our theory, which indicates that synchronization is promoted by a strong alignment of the natural frequencies with the left singular vectors corresponding to the largest singular values of the Laplacian matrix.

Erosion of synchronization: Coupling heterogeneity and network structure.

We study the dynamics of network-coupled phase oscillators in the presence of coupling frustration. It was recently demonstrated that in heterogeneous network topologies, the presence of coupling frustration causes perfect phase synchronization to become unattainable even in the limit of infinite coupling strength. Here, we consider the important case of heterogeneous coupling functions and extend previous results by deriving analytical predictions for the total erosion of synchronization. Our analytical results are given in terms of basic quantities related to the network structure and coupling frustration. In addition to fully heterogeneous coupling, where each individual interaction is allowed to be distinct, we also consider partially heterogeneous coupling and homogeneous coupling in which the coupling functions are either unique to each oscillator or identical for all network interactions, respectively. We demonstrate the validity of our theory with numerical simulations of multiple network models, and highlight the interesting effects that various coupling choices and network models have on the total erosion of synchronization. Finally, we consider some special network structures with well-known spectral properties, which allows us to derive further analytical results.

Optimal synchronization of complex networks.

We study optimal synchronization in networks of heterogeneous phase oscillators. Our main result is the derivation of a synchrony alignment function that encodes the interplay between network structure and oscillators' frequencies and that can be readily optimized. We highlight its utility in two general problems: constrained frequency allocation and network design. In general, we find that synchronization is promoted by strong alignments between frequencies and the dominant Laplacian eigenvectors, as well as a matching between the heterogeneity of frequencies and network structure.

Coexisting chaotic and multi-periodic dynamics in a model of cardiac alternans.

The spatiotemporal dynamics of cardiac tissue is an active area of research for biologists, physicists, and mathematicians. Of particular interest is the study of period-doubling bifurcations and chaos due to their link with cardiac arrhythmogenesis. In this paper, we study the spatiotemporal dynamics of a recently developed model for calcium-driven alternans in a one dimensional cable of tissue. In particular, we observe in the cable coexistence of regions with chaotic and multi-periodic dynamics over wide ranges of parameters. We study these dynamics using global and local Lyapunov exponents and spatial trajectory correlations. Interestingly, near nodes-or phase reversals-low-periodic dynamics prevail, while away from the nodes, the dynamics tend to be higher-periodic and eventually chaotic. Finally, we show that similar coexisting multi-periodic and chaotic dynamics can also be observed in a detailed ionic model.

Unidirectional pinning and hysteresis of spatially discordant alternans in cardiac tissue.

Spatially discordant alternans is a widely observed pattern of voltage and calcium signals in cardiac tissue that can precipitate lethal cardiac arrhythmia. Using spatially coupled iterative maps of the beat-to-beat dynamics, we explore this pattern's dynamics in the regime of a calcium-dominated period-doubling instability at the single-cell level. We find a novel nonlinear bifurcation associated with the formation of a discontinuous jump in the amplitude of calcium alternans at nodes separating discordant regions. We show that this jump unidirectionally pins nodes by preventing their motion away from the pacing site following a pacing rate decrease but permitting motion towards this site following a rate increase. This unidirectional pinning leads to strongly history-dependent node motion that is strongly arrhythmogenic.

Grass-roots optimization of coupled oscillator networks.

Despite the prevalence of biological and physical systems for which synchronization is critical, existing theory for optimizing synchrony depends on global information and does not sufficiently explore local mechanisms that enhance synchronization. Thus, there is a lack of understanding for the self-organized, collective processes that aim to optimize or repair synchronous systems, e.g., the dynamics of paracrine signaling within cardiac cells. Here we present "grass-roots" optimization of synchronization, which is a multiscale mechanism in which local optimizations of smaller subsystems cooperate to collectively optimize an entire system. Considering models of cardiac tissue and a power grid, we show that grass-roots-optimized systems are comparable to globally optimized systems, but they also have the added benefit of being robust to targeted attacks or subsystem islanding. Our findings motivate and support further investigation into the physics of local mechanisms that can support self-optimization for complex systems.

Quasiperiodic dynamics and a Neimark-Sacker bifurcation in nonlinear random walks on complex networks.

We study the dynamics of nonlinear random walks on complex networks. In particular, we investigate the role and effect of directed network topologies on long-term dynamics. While a period-doubling bifurcation to alternating patterns occurs at a critical bias parameter value, we find that some directed structures give rise to a different kind of bifurcation that gives rise to quasiperiodic dynamics. This does not occur for all directed network structure, but only when the network structure is sufficiently directed. We find that the onset of quasiperiodic dynamics is the result of a Neimark-Sacker bifurcation, where a pair of complex-conjugate eigenvalues of the system Jacobian pass through the unit circle, destabilizing the stationary distribution with high-dimensional rotations. We investigate the nature of these bifurcations, study the onset of quasiperiodic dynamics as network structure is tuned to be more directed, and present an analytically tractable case of a four-neighbor ring.

Universal scaling and phase transitions of coupled phase oscillator populations.

The Kuramoto model, which serves as a paradigm for investigating synchronization phenomena of oscillatory systems, is known to exhibit second-order, i.e., continuous, phase transitions in the macroscopic order parameter. Here we generalize a number of classical results by presenting a general framework for analytically capturing the critical scaling properties of the order parameter at the onset of synchronization. Using a self-consistent approach and constructing a characteristic function, we identify various phase transitions toward synchrony and establish scaling relations describing the asymptotic dependence of the order parameter on the coupling strength near the critical point. We find that the geometric properties of the characteristic function, which depends on the natural frequency distribution, determine the scaling properties of order parameter above criticality.

Low-dimensional dynamics of the Kuramoto model with rational frequency distributions.

The Kuramoto model is a paradigmatic tool for studying the dynamics of collective behavior in large ensembles of coupled dynamical systems. Over the past decade a great deal of progress has been made in analytical descriptions of the macroscopic dynamics of the Kuramoto model, facilitated by the discovery of Ott and Antonsen's dimensionality reduction method. However, the vast majority of these works relies on a critical assumption where the oscillators' natural frequencies are drawn from a Cauchy, or Lorentzian, distribution, which allows for a convenient closure of the evolution equations from the dimensionality reduction. In this paper we investigate the low-dimensional dynamics that emerge from a broader family of natural frequency distributions, in particular, a family of rational distribution functions. We show that, as the polynomials that characterize the frequency distribution increase in order, the low-dimensional evolution equations become more complicated, but nonetheless the system dynamics remain simple, displaying a transition from incoherence to partial synchronization at a critical coupling strength. Using the low-dimensional equations we analytically calculate the critical coupling strength corresponding to the onset of synchronization and investigate the scaling properties of the order parameter near the onset of synchronization. These results agree with calculations from Kuramoto's original self-consistency framework, but we emphasize that the low-dimensional equations approach used here allows for a true stability analysis categorizing the bifurcations.