Барлукова А.   Hubert F.   Honoré S.  

Microtubule aging and effect of microtubule targeted agents

Докладчик: Барлукова А.

Microtubules (MTs) are long tube polymers of tubulin, found throughout the cytoplasm. They are characterized by dynamic instabilities involved in a number of cellular processes, including cell division and migration. Microtubule-targeted drugs induce perturbation in their instabilities making them attractive for anti-cancer therapies.
Recent studies as [1] show that MTs age might play a crucial role in the effects of microtubule targeted drugs on MT instabilities. The aim of this work is to improve modeling of MT instability by introducing phenomenon of aging of MTs.
We propose a new deterministic mathematical model inspired by the work of P. Hinow et al. [2] to simulate the behavior of a MT population with presence of stabilizing and destabilizing drugs. The model couples transport equations with ordinary differential equations (ODE) with nonlocal terms endowed with suitable boundary conditions for both catastrophe and rescue. The mathematical model takes into account results of biological observations provided by the pharmacologist of our interdisciplinary research group [3].
New model allows us to demonstrate the pharmacological action of some anti-microtubule drugs on MT population through their influence on MT “aging” and, thus, on MT instabilities. Numerical results are in a good agreement with biological observations.

1. M.K. Gardner, M. Zanic, C. Gell, V. Bormuth, J. Howard. Depolymerizing Kinesins Kip3 and MCAK Shape Cellular Microtubule Architecture by Differential Control of Catastrophe. Cell 147, 1092–1103, November 23, 2011.
2. P. Hinow, V. Rezania, J.A. Tuzszynski. Continuous model for microtubule dynamics with catastrophe, rescue, and nucleation processes. Phys Rev E Stat Nonlin Soft Matter Phys. 80 (3 Pt 1): 031904, 2009.
3. S. Honoré, D. Braguer. Investigating microtubule dynamic instability using microtubule-targeting agents. Methods Mol. Biol. 777:245-60, 2011.

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