How the transition frequencies of microtubule dynamic instability (nucleation, catastrophe, and rescue) regulate microtubule dynamics in interphase and mitosis: analysis using a Monte Carlo computer simulation.

Abstract

Microtubules (MTs) in newt mitotic spindles grow faster than MTs in the interphase cytoplasmic microtubule complex (CMTC), yet spindle MTs do not have the long lengths or lifetimes of the CMTC microtubules. Because MTs undergo dynamic instability, it is likely that changes in the durations of growth or shortening are responsible for this anomaly. We have used a Monte Carlo computer simulation to examine how changes in the number of MTs and changes in the catastrophe and rescue frequencies of dynamic instability may be responsible for the cell cycle dependent changes in MT characteristics. We used the computer simulations to model interphase-like or mitotic-like MT populations on the basis of the dynamic instability parameters available from newt lung epithelial cells in vivo. We started with parameters that produced MT populations similar to the interphase newt lung cell CMTC. In the simulation, increasing the number of MTs and either increasing the frequency of catastrophe or decreasing the frequency of rescue reproduced the changes in MT dynamics measured in vivo between interphase and mitosis.

Dissociation of the Tubulin-sequestering and Microtubule Catastrophe-promoting Activities of Oncoprotein 18/Stathmin

“…Thus at steady state, less tubulin would be present in polymer, and this would give rise to an increased steady-state critical concentration in the presence of Op18. Modeling studies are consistent with this idea; increasing catastrophe frequency threefold reduced the mean length of microtubules to 30% of their original length and reduced the percentage of microtubules in polymer from ϳ63% to ϳ18% (Gliksman et al, 1993). Therefore, sequestering proteins and catastrophe-promoting proteins could each increase a steadystate critical concentration, suggesting that this is not a useful way to differentiate between these two destabilizing mechanisms.…”

G Protein α Subunits Activate Tubulin GTPase and Modulate Microtubule Polymerization Dynamics

“…The transition frequencies among the growing, shortening, and attenuated states are thought to be important in the regulation of microtubule dynamics in cells (13,14,45). Life history traces of several microtubules in the absence (panel A) or presence (panel B) of G i1 ␣ are shown in Fig.…”

Insights into cytoskeletal behavior from computational modeling of dynamic microtubules in a cell-like environment

“…Significant efforts have been made to predict and explain MT behavior using both deterministic models (systems of interacting equations) and stochastic simulations (Markov chain/Monte Carlo approaches) (e.g. Bayley et al, 1989;Bolterauer et al, 1999;Dogterom and Leibler, 1993;Flyvbjerg et al, 1996a;Freed, 2002;Gliksman et al, 1993;Govindan and Spillman, Jr, 2004;Hill and Chen, 1984;VanBuren et al, 2002).…”