title: Modeling the effects of drug binding on the dynamic instability of microtubules.
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.
authors.affiliation: Department of Mathematical Sciences, University of Wisconsin-Milwaukee, PO Box 413, Milwaukee, WI 53201, USA. hinow@uwm.edu
authors.forename: Peter
authors.initials: P
authors.lastname: Hinow
authors.forename: Vahid
authors.initials: V
authors.lastname: Rezania
authors.forename: Manu
authors.initials: M
authors.lastname: Lopus
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Jordan
authors.forename: Jack A
authors.initials: JA
authors.lastname: Tuszyński
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D008453:Maytansine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D012617:Sea Urchins; D013269:Stochastic Processes; D014404:Tubulin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014404:Tubulin; D008453:Maytansine; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate