Modeling the effects of drug binding on the dynamic instability of microtubules.
Phys Biol
; 8(5): 056004, 2011 Oct.
Article
en En
| MEDLINE
| ID: mdl-21836336
ABSTRACT
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Maitansina
/
Microtúbulos
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Phys Biol
Asunto de la revista:
BIOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos