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Phys Biol
2011 Oct 01;85:056004. doi: 10.1088/1478-3975/8/5/056004.
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Modeling the effects of drug binding on the dynamic instability of microtubules.
Hinow P
,
Rezania V
,
Lopus M
,
Jordan MA
,
Tuszyński JA
.
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We propose a stochastic model that accounts for the growth, catastrophe and rescue processes of steady-state microtubules assembled from MAP-free tubulin in the possible presence of a microtubule-associated drug. As an example of the latter, we both experimentally and theoretically study the perturbation of microtubule dynamic instability by S-methyl-D-DM1, a synthetic derivative of the microtubule-targeted agent maytansine and a potential anticancer agent. Our model predicts that among the drugs that act locally at the microtubule tip, primary inhibition of the loss of GDP tubulin results in stronger damping of microtubule dynamics than inhibition of GTP tubulin addition. On the other hand, drugs whose action occurs in the interior of the microtubule need to be present in much higher concentrations to have visible effects.
Antal,
Dynamics of an idealized model of microtubule growth and catastrophe.
2007, Pubmed
Antal,
Dynamics of an idealized model of microtubule growth and catastrophe.
2007,
Pubmed
Bayley,
A lateral cap model of microtubule dynamic instability.
1989,
Pubmed
Bennett,
Structural mass spectrometry of the alpha beta-tubulin dimer supports a revised model of microtubule assembly.
2009,
Pubmed
Bolterauer,
Microtubules: strange polymers inside the cell.
1999,
Pubmed
Bolterauer,
Models of assembly and disassembly of individual microtubules: stochastic and averaged equations.
1999,
Pubmed
Brun,
A theory of microtubule catastrophes and their regulation.
2009,
Pubmed
Carlier,
Synchronous oscillations in microtubule polymerization.
1987,
Pubmed
Davé,
A molecular and structural mechanism for G protein-mediated microtubule destabilization.
2011,
Pubmed
Dimitrov,
Detection of GTP-tubulin conformation in vivo reveals a role for GTP remnants in microtubule rescues.
2008,
Pubmed
Flyvbjerg,
Microtubule dynamics: Caps, catastrophes, and coupled hydrolysis.
1996,
Pubmed
Flyvbjerg,
Stochastic dynamics of microtubules: A model for caps and catastrophes.
1994,
Pubmed
Gregoretti,
Insights into cytoskeletal behavior from computational modeling of dynamic microtubules in a cell-like environment.
2006,
Pubmed
Hinow,
Continuous model for microtubule dynamics with catastrophe, rescue, and nucleation processes.
2009,
Pubmed
Howard,
Growth, fluctuation and switching at microtubule plus ends.
2009,
Pubmed
Jackson,
Nucleation and the kinetics of microtubule assembly.
1980,
Pubmed
Jordan,
How do microtubule-targeted drugs work? An overview.
2007,
Pubmed
Lin,
Effects of inhibitors of tubulin polymerization on GTP hydrolysis.
1981,
Pubmed
Lopus,
Antibody-DM1 conjugates as cancer therapeutics.
2011,
Pubmed
Lopus,
Maytansine and cellular metabolites of antibody-maytansinoid conjugates strongly suppress microtubule dynamics by binding to microtubules.
2010,
Pubmed
Mandelkow,
Spatial patterns from oscillating microtubules.
1989,
Pubmed
Matzavinos,
A stochastic analysis of actin polymerization in the presence of twinfilin and gelsolin.
2007,
Pubmed
Mishra,
Dynamic instability of microtubules: effect of catastrophe-suppressing drugs.
2005,
Pubmed
Mitchison,
Dynamic instability of microtubule growth.
1984,
Pubmed
Mozziconacci,
Tubulin dimers oligomerize before their incorporation into microtubules.
2008,
Pubmed
Oroudjev,
Maytansinoid-antibody conjugates induce mitotic arrest by suppressing microtubule dynamic instability.
2010,
Pubmed
Rezania,
Microtubule assembly of isotypically purified tubulin and its mixtures.
2008,
Pubmed
VanBuren,
Estimates of lateral and longitudinal bond energies within the microtubule lattice.
2002,
Pubmed
VanBuren,
Mechanochemical model of microtubule structure and self-assembly kinetics.
2005,
Pubmed
Walker,
Dynamic instability of individual microtubules analyzed by video light microscopy: rate constants and transition frequencies.
1988,
Pubmed
Widdison,
Semisynthetic maytansine analogues for the targeted treatment of cancer.
2006,
Pubmed
Yenjerla,
The neuroprotective peptide NAP does not directly affect polymerization or dynamics of reconstituted neural microtubules.
2010,
Pubmed
Yenjerla,
Analysis of dynamic instability of steady-state microtubules in vitro by video-enhanced differential interference contrast microscopy with an appendix by Emin Oroudjev.
2010,
Pubmed
,
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