Bistable networks

Prompted by the recent growing evidence of oscillatory behavior involving MAPK cascades we present a systematic approach of analyzing models and elucidating the nature of biochemical oscillations based on reaction network theory. In particular, we formulate a minimal biochemically consistent mass action subnetwork of the Huang-Ferrell model of the MAPK signalling that provides an oscillatory response when a parameter controlling the activation of the top-tier kinase is varied. Such dynamics are either intertwined with or separated from the earlier found bistable/hysteretic behavior in this model...

Phosphorylation, the enzyme-mediated addition of a phosphate group to a molecule, is a ubiquitous chemical mechanism in biology. Multisite phosphorylation, the addition of phosphate groups to multiple sites of a single molecule, may be distributive or processive. Distributive systems, which require an enzyme and substrate to bind several times in order to add multiple phosphate groups, can be bistable. Processive systems, in contrast, require only one binding to add all phosphate groups, and were recently shown to be globally stable...

Living systems rely on complex networks of chemical reactions to control the concentrations of molecules in space and time. Despite the enormous complexity in biological networks, it is possible to identify network motifs that lead to functional outputs such as bistability or oscillations. One of the greatest challenges in chemistry is the creation of such functionality from chemical reactions. A key limitation is our lack of understanding of how molecular structure impacts on the dynamics of chemical reaction networks, preventing the design of networks that are robust (i...

Measuring the spatiotemporal complexity of cortical responses to direct perturbations provides a reliable index of the brain's capacity for consciousness in humans under both physiological and pathological conditions. Upon loss of consciousness, the complex pattern of causal interactions observed during wakefulness collapses into a stereotypical slow wave, suggesting that cortical bistability may play a role. Bistability is mainly expressed in the form of slow oscillations, a default pattern of activity that emerges from cortical networks in conditions of functional or anatomical disconnection...

We present theoretical and experimental studies on pattern formation with bistable dynamical units coupled in a star network configuration. By applying a localized perturbation to the central or the peripheral elements, we demonstrate the subsequent spreading, pinning, or retraction of the activations; such analysis enables the characterization of the formation of stationary patterns of localized activity. The results are interpreted with a theoretical analysis of a simplified bistable reaction-diffusion model...

The combination of bistability and noise is ubiquitous in complex systems, from biology to social interactions, and has important implications for their functioning and resilience. Here we use a simple three-state dynamical process, in which nodes go from one pole to another through an intermediate state, to show that noise can induce polarization switching in bistable systems if dynamical correlations are significant. In large, fully connected networks, where dynamical correlations can be neglected, increasing noise yields a collapse of bistability to an unpolarized configuration where the three possible states of the nodes are equally likely...

Intrinsic tumor-suppressive mechanisms protect normal cells against aberrant proliferation. Although cellular signaling pathways engaged in tumor repression have been largely identified, how they are orchestrated to fulfill their function still remains elusive. Here, we built a tumor-suppressive network model composed of three modules responsible for the regulation of cell proliferation, activation of p53, and induction of apoptosis. Numerical simulations show a rich repertoire of network dynamics when normal cells are subject to serum stimulation and adenovirus E1A overexpression...

Signal transduction within biological cells is governed by networks of interacting proteins. Communication between these proteins is mediated by signaling molecules which bind to receptors and induce stochastic transitions between different conformational states. Signaling is typically a cooperative process which requires the occurrence of multiple binding events so that reaction rates have a nonlinear dependence on the amount of signaling molecule. It is this nonlinearity that endows biological signaling networks with robust switchlike properties which are critical to their biological function...

Optical nonlinearities, such as thermo-optic mechanisms and free-carrier dispersion, are often considered unwelcome effects in silicon-based resonators and, more specifically, optomechanical cavities, since they affect, for instance, the relative detuning between an optical resonance and the excitation laser. Here, we exploit these nonlinearities and their intercoupling with the mechanical degrees of freedom of a silicon optomechanical nanobeam to unveil a rich set of fundamentally different complex dynamics...

Integrative and conjugative elements (ICEs) are widespread mobile DNA that transmit both vertically, in a host-integrated state, and horizontally, through excision and transfer to new recipients. Different families of ICEs have been discovered with more or less restricted host ranges, which operate by similar mechanisms but differ in regulatory networks, evolutionary origin and the types of variable genes they contribute to the host. Based on reviewing recent experimental data, we propose a general model of ICE life style that explains the transition between vertical and horizontal transmission as a result of a bistable decision in the ICE-host partnership...

Bistability has important implications in signaling pathways, since it indicates a potential cell decision between alternative outcomes. We present two approaches developed in the framework of the Chemical Reaction Network Theory for easy and efficient search of multiple steady state behavior in signaling networks (both with and without mass conservation), and apply them to search for sources of bistability at different levels of the interferon signaling pathway. Different type I interferon subtypes and/or doses are known to elicit differential bioactivities (ranging from antiviral, antiproliferative to immunomodulatory activities)...

Nitrogen is cycled throughout ecosystems by a suite of biogeochemical processes. The high complexity of the nitrogen cycle resides in an intricate interplay between reversible biochemical pathways alternatively and specifically activated in response to diverse environmental cues. Despite aggressive research, how the fundamental nitrogen biochemical processes are assembled and maintained in fluctuating soil redox conditions remains elusive. Here, we address this question using a kinetic modelling approach coupled with dynamical systems theory and microbial genomics...

Various cellular decision making processes are regulated by bistable switches that take graded input signals and convert them to binary all-or-none responses. Traditionally, a bistable switch generated by a positive feedback loop is characterized either by a hysteretic signal response curve with two distinct signaling thresholds or by characterizing the bimodality of the response distribution in the bistable region. To identify the intrinsic bistability of a feedback regulated network, here we propose that bistability can be determined by correlating higher order moments and cumulants (≥2) of the joint steady state distributions of two components connected in a positive feedback loop...

The Notch pathway plays a vital role in determining whether cells in the intestinal epithelium adopt a secretory or an absorptive phenotype. Cell fate specification is coordinated via Notch's interaction with the canonical Wnt pathway. Here, we propose a new mathematical model of the Notch and Wnt pathways, in which the Hes1 promoter acts as a hub for pathway crosstalk. Computational simulations of the model can assist in understanding how healthy intestinal tissue is maintained, and predict the likely consequences of biochemical knockouts upon cell fate selection processes...

Binocular rivalry is a phenomenon in which perception spontaneously shifts between two different images that are dichoptically presented to the viewer. By elucidating the cortical networks responsible for these stochastic fluctuations in perception, we can potentially learn much about the neural correlates of visual awareness. We obtained concurrent EEG-fMRI data for a group of 20 healthy human subjects during the continuous presentation of dichoptic visual stimuli. The two eyes' images were tagged with different temporal frequencies so that eye specific steady-state visual evoked potential (SSVEP) signals could be extracted from the EEG data for direct comparison with changes in fMRI BOLD activity associated with binocular rivalry...

BACKGROUND: Positive and negative feedback loops are ubiquitous motifs in biochemical signaling pathways. The mitogen-activated protein kinase (MAPK) pathway module is part of many distinct signaling networks and comprises several of these motifs, whose functioning depends on the cell line at hand and on the particular context. The maintainance of specificity of the response of the MAPK module to distinct stimuli has become a key paradigm especially in PC-12 cells, where the same module leads to different cell fates, depending on the stimulating growth factor...

Bistability and bifurcation, found in a wide range of biochemical networks, are central to the proper function of living systems. We investigate herein recent model systems that show bistable behavior based on nonenzymatic self-replication reactions. Such models were used before to investigate catalytic growth, chemical logic operations, and additional processes of self-organization leading to complexification. By solving for their steady-state solutions by using various analytical and numerical methods, we analyze how and when these systems yield bistability and bifurcation and discover specific cases and conditions producing bistability...

Peroxidase-oxidase is an enzymatic reaction that can exhibit dynamical scenarios such as bistability, sustained oscillations, and Shilnikov chaos. In this work, we apply the chemical reaction network theory approach to find kinetic constants such that the associated mass action kinetics ordinary differential equations induced by three four dimensional structurally different enzymatic reaction systems can support the same steady states for several chemical species despite differences in their chemical nature...

We study the behavior of a minimal model of synaptically sustained persistent activity that consists of two quadratic integrate-and-fire neurons mutually coupled via excitatory synapses. Importantly, each of the neurons is excitable, as opposed to an oscillator; hence when uncoupled it sits at a subthreshold rest state. When the constituent neurons are mutually coupled via sufficiently strong fast excitatory synapses, the system demonstrates bistability between a fixed point (quiescent background state) and a limit cycle (memory state with synaptically driven spiking activity)...

BACKGROUND: The skin barrier acts as the first line of defense against constant exposure to biological, microbial, physical, and chemical environmental stressors. Dynamic interplay between defects in the skin barrier, dysfunctional immune responses, and environmental stressors are major factors in the development of atopic dermatitis (AD). A systems biology modeling approach can yield significant insights into these complex and dynamic processes through integration of prior biological data...