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A minimal "push-pull" bistability model explains oscillations between quiescent and proliferative cell states
Sandeep Krishna1, Sunil Laxman2
1Simons Centre for the Study of Living Machines, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.
This study introduces a simple model to explain how cells switch between resting and active growth states. The model is based on the availability of a central metabolic resource, which acts as a regulator. The researchers use a concept called hysteresis to show that cells remember their current state and resist switching. This memory, combined with the availability of the resource, creates a push-pull effect that leads to oscillations. The model is tested against observed metabolic cycles in yeast and successfully reproduces these patterns. The researchers argue that a single resource is enough to drive these transitions. This approach simplifies existing models and provides a new framework for understanding how metabolism controls cell state changes.
Area of Science:
- Cell cycle regulation in systems biology
- Metabolic oscillations in microbial physiology
Background:
Cellular transitions between quiescence and proliferation remain poorly understood in the context of metabolic control. While prior research has shown that metabolic cycles influence cell state, the mechanisms linking resource availability to oscillatory behavior are unclear. No prior work had resolved how a single metabolic resource might drive these transitions. Existing models often require multiple interacting components, but this gap motivated the search for a simpler explanation. The yeast metabolic cycle offers a natural system to study such oscillations. Researchers have observed periodic shifts in oxygen consumption, but the underlying regulatory framework remains debated. This uncertainty drove the development of a model based on bistability and hysteresis. The need for a minimal framework to explain complex oscillations remains a key challenge.
Purpose Of The Study:
This study aimed to develop a minimal model for oscillations between quiescent and growth states in cells. The focus was on metabolic resource availability as the key driver of these transitions. The researchers sought to explain how a single resource could regulate oscillatory behavior. They proposed a model based on bistability and hysteresis to capture the memory of cell states. The motivation was to simplify existing models that require multiple regulators. The model was designed to reflect observed metabolic cycles in yeast. The goal was to show that a single resource could suffice for oscillatory regulation. This approach could clarify the role of metabolic control in cell state transitions.
Main Methods:
The researchers used a relaxation oscillator model to simulate transitions between quiescent and growth states. They incorporated hysteresis to represent the memory of each cell state. The model included switching rates between states based on resource availability. They considered growth rates and metabolic resource dynamics as key variables. The model was designed to be minimal, avoiding unnecessary components. They tested the model against observed metabolic oscillations in yeast. The framework relied on a central metabolite as the regulatory component. The model was validated by its ability to reproduce oscillatory behavior.
Main Results:
The model successfully simulated oscillations between quiescent and growth states using a single metabolic resource. The researchers found that hysteresis was essential for maintaining state memory. Switching rates were shown to depend on resource availability. The model explained how a central metabolite could regulate transitions. The results suggest that a single resource can drive oscillatory behavior. The model reproduced observed metabolic cycles in yeast. The researchers identified a specific metabolite as a potential controller. The model demonstrated that committed transitions are sufficient for oscillations.
Conclusions:
The authors propose that a minimal model based on a single metabolic resource can explain oscillations between cell states. They suggest that hysteresis and switching rates are necessary for the model to function. The model demonstrates that a central metabolite can regulate transitions. The researchers argue that this approach simplifies existing models. The model aligns with observed metabolic cycles in yeast. The findings suggest that committed transitions are sufficient for oscillations. The authors propose that this framework could apply to other systems. The model provides a new perspective on metabolic regulation of cell states.
Frequently Asked Questions
The model suggests that a central metabolic resource regulates transitions through hysteresis and switching rates.
The model uses hysteresis to represent the memory of whether a cell is in a quiescent or growth state.
The researchers argue that a central metabolite can control switching rates between states without additional regulators.
The central metabolite is proposed as the controller of transitions between quiescent and growth states.
The model shows that committed transitions are sufficient to reproduce observed metabolic oscillations.
The authors suggest that a single metabolic resource can regulate oscillations between cell states.