Mapping the mitotic clock by phase perturbation

Area of Science:

• Cell Biology
• Biophysics
• Mathematical Biology

Background:

• Cell cycle progression is tightly regulated.
• External perturbations can disrupt cell cycle timing.
• Understanding cell cycle dynamics is crucial for various biological processes.

Purpose of the Study:

• To investigate the effects of perturbations on synchronized V79 cell cycles.
• To develop and validate a mathematical model for cell cycle regulation.
• To explain quantized generation times and population desynchronization.

Main Methods:

• Synchronized V79 cells were perturbed using serum, heat shock, and ionizing radiation.
• Phase-response curves were generated to analyze cell division timing.
• A two-component oscillator model was developed and simulated.
• Model parameters were fitted using experimental data on phase response, desynchronization, and generation times.

Main Results:

• Perturbations induced characteristic biphasic phase-response curves (advances and delays).
• A two-component oscillator model accurately simulated experimental phase-response curves.
• The model explained quantized generation times within a negative exponential distribution.
• Model parameters derived from phase response and desynchronization data also predicted generation time distributions.

Conclusions:

• A two-component oscillator model provides a robust framework for understanding cell cycle dynamics.
• The model accounts for observed cell cycle responses to perturbations and variations in generation times.
• This approach offers insights into the mechanisms underlying cell cycle regulation and stochasticity.