Switchable Genetic Oscillator Operating in Quasi-Stable Mode

Ring topologies of repressing genes have qualitatively different long-term dynamics if the number of genes is odd (they oscillate) or even (they exhibit bistability). However, these attractors may not fully explain the observed behavior in transient and stochastic environments such as the cell. We show here that even repressilators possess quasi-stable, travelling-wave periodic solutions that are reachable, long-lived and robust to parameter changes. These solutions underlie the sustained oscillations observed in even rings in the stochastic regime, even if these circuits are expected to behave as switches. The existence of such solutions can also be exploited for control purposes: operation of the system around the quasi-stable orbit allows us to turn on and off the oscillations reliably and on demand. We illustrate these ideas with a simple protocol based on optical interference that can induce oscillations robustly both in the stochastic and deterministic regimes.Comment: 24 pages, 5 main figure

Numerical analysis of a mechanotransduction dynamical model reveals homoclinic bifurcations of extracellular matrix mediated oscillations of the mesenchymal stem cell fate

We perform one and two-parameter numerical bifurcation analysis of a mechanotransduction model approximating the dynamics of mesenchymal stem cell differentiation into neurons, adipocytes, myocytes and osteoblasts. For our analysis, we use as bifurcation parameters the stiffness of the extracellular matrix and parameters linked with the positive feedback mechanisms that up-regulate the production of the YAP/TAZ transcriptional regulators (TRs) and the cell adhesion area. Our analysis reveals a rich nonlinear behaviour of the cell differentiation including regimes of hysteresis and multistability, stable oscillations of the effective adhesion area, the YAP/TAZ TRs and the PPAR$\gamma$ receptors associated with the adipogenic fate, as well as homoclinic bifurcations that interrupt relatively high-amplitude oscillations abruptly. The two-parameter bifurcation analysis of the Andronov-Hopf points that give birth to the oscillating patterns predicts their existence for soft extracellular substrates ($<1kPa$), a regime that favours the neurogenic and the adipogenic cell fate. Furthermore, in these regimes, the analysis reveals the presence of homoclinic bifurcations that result in the sudden loss of the stable oscillations of the cell-substrate adhesion towards weaker adhesion and high expression levels of the gene encoding Tubulin beta-3 chain, thus favouring the phase transition from the adipogenic to the neurogenic fate

Design of time delayed chaotic circuit with threshold controller

A novel time delayed chaotic oscillator exhibiting mono- and double scroll complex chaotic attractors is designed. This circuit consists of only a few operational amplifiers and diodes and employs a threshold controller for flexibility. It efficiently implements a piecewise linear function. The control of piecewise linear function facilitates controlling the shape of the attractors. This is demonstrated by constructing the phase portraits of the attractors through numerical simulations and hardware experiments. Based on these studies, we find that this circuit can produce multi-scroll chaotic attractors by just introducing more number of threshold values.Comment: 21 pages, 12 figures; Submitted to IJB