Section: New Results

Data assimilation and modeling of cell division mechanism

Participants : Ancageorgiana Caranfil, Charles Kervrann.

In this work, we focus on the dynamics of the spindle during cell division mechanism. We aim at understanding the role and interaction of the molecular key players at different scales, and their individual and collective impact on the global mechanism at the cell level. Our approach consists in creating a biophysical model for this mechanism, and uses data assimilation to adjust the model and optimally integrate the information from the observations. The overall spindle behavior is led by the spindle poles behavior. We thus proposed a new biophysical model for the spindle pole functioning during anaphase, that explains the oscillatory behavior with a minimum number of parameters. By mathematically analyzing our model, we confirmed some previous findings, such as the existence of a threshold number of active force-generator motors required for the onset of oscillations. We also confirmed that the monotonic increase of motor activity accounts for their build-up and die-down. We determined boundaries for the motor activity-related parameters for these oscillations to happen. This also allowed us to describe the influence of the number of motors, as well as physical parameters related to viscosity or string-like forces, on features such as the amplitude and frequency of oscillations. Lastly, by using a Bayesian approach to confront our model to experimental data, we were able to estimate distributions for our biological and biophysical parameters. A statistical reduction model approach was preliminary applied to select the most influential model parameters. These results give us insights on variations in spindle behavior during anaphase in asymmetric division, and provide means of prediction for phenotypes related to misguided asymmetric division. Data assimilation will be further used to properly combine the information given by our model and the experimental data.

Collaborators: Yann Le Cunff and Jacques Pécréaux (IGDR Institute of Genetics & Development of Rennes).

Figure 10. A. Cell division observed by fluorescence microscopy. B. and C. Tracking of the two spindle pole (anterior in red and posterior in blue). Oscillations of the poles during metaphase and anaphase. D. Simulation of oscillations using our model. E. Fitting of experimental data (in blue), and the two estimated curves with our method (minimum estimator in red, and mean estimator in green).