A computational model of mutual antagonism in the mechano-signaling network of RhoA and nitric oxide

Background RhoA is a master regulator of cytoskeletal contractility, while nitric oxide (NO) is a master regulator of relaxation, e.g., vasodilation. There are multiple forms of cross-talk between the RhoA/ROCK pathway and the eNOS/NO/cGMP pathway, but previous work has not studied their interplay at a systems level. Literature review suggests that the majority of their cross-talk interactions are antagonistic, which motivates us to ask whether the RhoA and NO pathways exhibit mutual antagonism in vitro, and if so, to seek the theoretical implications of their mutual antagonism. Results Experiments found mutual antagonism between RhoA and NO in epithelial cells. Since mutual antagonism is a common motif for bistability, we sought to explore through theoretical simulations whether the RhoA-NO network is capable of bistability. Qualitative modeling showed that there are parameters that can cause bistable switching in the RhoA-NO network, and that the robustness of the bistability would be increased by positive feedback between RhoA and mechanical tension. Conclusions We conclude that the RhoA-NO bistability is robust enough in silico to warrant the investment of further experimental testing. Tension-dependent bistability has the potential to create sharp concentration gradients, which could contribute to the localization and self-organization of signaling domains during cytoskeletal remodeling and cell migration.

Optical bistability in reflection from multilayer metal-dielectric structure with Kerr nonlinearity

Both static and dynamic characteristics of light reflected from a specially designed multilayer metal-dielectric structure with Kerr nonlinearity have been studied in this work. Various regimes of nonlinear reflection from the structure have been demonstrated, including bistable switching between low and high reflection states, which occurs at low intensity of the incident light due to a significant enhancement in the optical field in the nonlinear layer under conditions of total internal reflection. This nonlinear structure has been proposed to use as an optically controlled intracavity laser modulator.

Reversible photo/thermal stimuli-responsive electrical bistability performance in supramolecular co-crystals accompanied by crystalline-to-amorphous transformations

A co-crystal-based device exhibits reversibly stimuli-responsive switchable conductivity states, and its photo/thermal responsive electrically bistable switching mechanism was proposed.

Stochastic activation and bistability in a Rab GTPase regulatory network

Rab GTPases are the central regulators of intracellular traffic. Their function relies on a conformational change triggered by nucleotide exchange and hydrolysis. While this switch is well understood for an individual protein, how Rab GTPases collectively transition between states to generate a biochemical signal in space and time is unclear. Here, we combine in vitro reconstitution experiments with theoretical modeling to study a minimal Rab5 activation network. We find that positive feedback in this network gives rise to bistable switching of Rab5 activation and provide evidence that controlling the inactive population of Rab5 on the membrane can shape the network response. Together, our findings reveal new insights into the non-equilibrium properties and general principles of biochemical signaling networks underlying the spatiotemporal organization of the cell.

Molecular Mechanisms Driving Bistable Switch Behavior in Xylem Cell Differentiation

SummaryPlant xylem cells conduct water and mineral nutrients. Although most plant cells are totipotent, xylem cells are unusual and undergo terminal differentiation. Many genes regulating this process are well characterized, including the VASCULAR-RELATED NAC DOMAIN7 (VND7), MYB46 and MYB83 transcription factors which are proposed to act in interconnected feed-forward loops. Much less is known regarding the dynamic behavior underlying the terminal transition to xylem cell differentiation. Here we utilize whole root and single cell data to mathematically model this relationship. These provide evidence for VND7 regulating bistable switching of cells in the root to a xylem cell identity, with additional features of hysteresis. We further determine that although MYB46 responds to VND7 induction, it is not inherently involved in executing the binary switch. A novel regulatory architecture is proposed that involves four downstream targets of VND7 that act in a cycle. These data provide an important model to study the emergent properties that may give rise to totipotency relative to terminal differentiation and reveal novel xylem cell subtypes.