title: Mechanical and functional properties of epothilone-stabilized microtubules.
abstract: Using a suite of biophysical tools, we assess the mechanical, structural, and functional properties of microtubules (MTs) stabilized by the chemotherapeutic compounds epothilone-A, epothilone-B, and taxol in vitro. We demonstrate that MTs stabilized by epothilone-A or epothilone-B are competent to bind tau proteins and support kinesin translocation. Kinesin speed is sensitive not only to the type of small molecule stabilizer used but also to the presence of the essential MT-associated protein tau. Epothilone-stabilized MTs are substantially less stiff than taxol-stabilized MTs. The addition of tau proteins to MTs stabilized by either epothilone compound or taxol further reduces stiffness. Taken together, these results suggest that small molecule stabilizers do not simply stabilize a "native" MT structure, but rather they modulate the structure, function, and mechanics of the MTs they bind. This may have important consequences to the therapeutic use of these agents in cancer chemotherapies.
authors.affiliation: Department of Materials, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Yu
authors.forename: Veronica
authors.initials: V
authors.lastname: Pessino
authors.forename: Steve
authors.initials: S
authors.lastname: Kuei
authors.forename: Megan T
authors.initials: MT
authors.lastname: Valentine
mesh_terms: D000818:Animals; D002417:Cattle; D034261:Epothilones / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism; D009369:Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism; D017239:Paclitaxel / Q000737:chemistry / Q000378:metabolism; D055550:Protein Stability; D050257:Tubulin Modulators / Q000627:therapeutic use; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D034261:Epothilones; C054369:MAPT protein, human; D050257:Tubulin Modulators; D016875:tau Proteins; C093787:epothilone A; D017239:Paclitaxel; C093788:epothilone B