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Microtubules (MTs) are protein polymers that exhibit a unique type of behavior referred to as dynamic instability. That is, they undergo periods of growth (through the addition of GTP-tubulin) and shortening (through the subtraction of GDP-tubulin). Shortening events are very fast, where this transition is referred to as a catastrophe. There are many processes that regulate MT dynamic instability, however, recent experiments show that MT dynamics may be highly regulated by a MTs age, where young MTs are less likely to undergo shortening events than older ones. In this paper, we develop a novel modeling approach to describe how the age of a MT affects its dynamic properties. In particular, we extend on a previously developed model that describes MT dynamics, by proposing a new concept for GTP-tubulin hydrolysis (the process by which newly incorporated GTP-tubulin is hydrolyzed to lower energy GDP-tubulin). In particular, we assume that hydrolysis is mainly vectorial, age-dependent and delayed according to the GTP-tubulin incorporation into the MT. Through numerical simulation, we are able to show how MT age affects certain properties that define MT dynamics. For example, simulations illustrate how the aging process leads to an increase in the rate of GTP-tubulin hydrolysis for older MTs, as well as increases in catastrophe frequency. Also, since it has been found that MT dynamic instability is affected by chemotherapy microtubule-targeting agents (MTAs), we highlight the fact that our model can be used to investigate the action of MTAs on MT dynamics by varying certain model parameters.
Barlukova, Ayuna 1 ; White, Diana 1 ; Henry, Gérard 1 ; Honoré, Stéphane 1 ; Hubert, Florence 1
@article{M2AN_2018__52_6_2433_0,
author = {Barlukova, Ayuna and White, Diana and Henry, G\'erard and Honor\'e, St\'ephane and Hubert, Florence},
title = {Mathematical modeling of microtubule dynamic instability: new insight into the link between gtp-hydrolysis and microtubule aging},
journal = {ESAIM: Mathematical Modelling and Numerical Analysis },
pages = {2433--2456},
publisher = {EDP-Sciences},
volume = {52},
number = {6},
year = {2018},
doi = {10.1051/m2an/2017025},
zbl = {1415.92078},
mrnumber = {3909806},
language = {en},
url = {http://geodesic.mathdoc.fr/articles/10.1051/m2an/2017025/}
}
TY - JOUR AU - Barlukova, Ayuna AU - White, Diana AU - Henry, Gérard AU - Honoré, Stéphane AU - Hubert, Florence TI - Mathematical modeling of microtubule dynamic instability: new insight into the link between gtp-hydrolysis and microtubule aging JO - ESAIM: Mathematical Modelling and Numerical Analysis PY - 2018 SP - 2433 EP - 2456 VL - 52 IS - 6 PB - EDP-Sciences UR - http://geodesic.mathdoc.fr/articles/10.1051/m2an/2017025/ DO - 10.1051/m2an/2017025 LA - en ID - M2AN_2018__52_6_2433_0 ER -
%0 Journal Article %A Barlukova, Ayuna %A White, Diana %A Henry, Gérard %A Honoré, Stéphane %A Hubert, Florence %T Mathematical modeling of microtubule dynamic instability: new insight into the link between gtp-hydrolysis and microtubule aging %J ESAIM: Mathematical Modelling and Numerical Analysis %D 2018 %P 2433-2456 %V 52 %N 6 %I EDP-Sciences %U http://geodesic.mathdoc.fr/articles/10.1051/m2an/2017025/ %R 10.1051/m2an/2017025 %G en %F M2AN_2018__52_6_2433_0
Barlukova, Ayuna; White, Diana; Henry, Gérard; Honoré, Stéphane; Hubert, Florence. Mathematical modeling of microtubule dynamic instability: new insight into the link between gtp-hydrolysis and microtubule aging. ESAIM: Mathematical Modelling and Numerical Analysis , Tome 52 (2018) no. 6, pp. 2433-2456. doi: 10.1051/m2an/2017025
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