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Alex Mogliner
Department of Mathematics
University of California


Monte Carlo Simulations and Probabilistic Analysis Shed Light on how Microtubules Search in Space

Mitosis is the process of segregation of chromosomes before cell division. Before the chromosomes can be moved, they have to be attached to the opposite poles of the cell through microtubules, dynamic polymers that grow and shrink rapidly and repeatedly probing space and searching for the chromosomes. Attachment to the chromosomes stabilizes microtubules and is a basis for the proper cell division. This process, termed Search and Capture, is time consuming and is often the bottleneck for the cell division. In this work, using mathematical modeling and stochastic simulations, we show that without any bias toward the chromosomes, Search and Capture is not efficient enough to explain experimentally measured mitosis duration. We propose that a spatial chemical gradient stabilizes microtubules in the vicinity of the chromosomes, therefore introducing a bias in the Search and Capture process. We show mathematically that the biased Search and Capture is efficient enough to explain experimental results . To test model predictions, we measured the mitosis duration in mutant cells. Our experimental results confirm the model predictions. The model also suggests that the cell fine-tunes a number of parameters to optimize the process, and that the time for Search and Capture depends littlew on the chromosome number. The last conclusion has important implication for cancer cells.



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