Nature communications

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2041-1723912018Sep03Nature communicationsNat CommunThe mitotic spindle is chiral due to torques within microtubule bundles.35713571357110.1038/s41467-018-06005-7Mitosis relies on forces generated in the spindle, a micro-machine composed of microtubules and associated proteins. Forces are required for the congression of chromosomes to the metaphase plate and their separation in anaphase. However, besides forces, torques may exist in the spindle, yet they have not been investigated. Here we show that the spindle is chiral. Chirality is evident from the finding that microtubule bundles in human spindles follow a left-handed helical path, which cannot be explained by forces but rather by torques. Kinesin-5 (Kif11/Eg5) inactivation abolishes spindle chirality. Our theoretical model predicts that bending and twisting moments may generate curved shapes of bundles. We found that bundles turn by about -2 deg µm^-1 around the spindle axis, which we explain by a twisting moment of roughly -10 pNµm. We conclude that torques, in addition to forces, exist in the spindle and determine its chiral architecture.NovakMajaMDepartment of Physics, Faculty of Science, University of Zagreb, Bijenička cesta 32, 10000, Zagreb, Croatia.Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia.PolakBrunoBDivision of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia.SimunićJurajJ0000-0002-3058-7311Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia.BobanZvonimirZDepartment of Physics, Faculty of Science, University of Zagreb, Bijenička cesta 32, 10000, Zagreb, Croatia.KuzmićBarbaraBDivision of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia.ThomaeAndreas WAWWalter Brendel Centre of Experimental Medicine and Core Facility Bioimaging at the Biomedical Center, University of Munich, 82152, Planegg-Martinsried, Germany.TolićIva MIM0000-0003-1305-7922Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia. tolic@irb.hr.PavinNenadN0000-0002-4313-1081Department of Physics, Faculty of Science, University of Zagreb, Bijenička cesta 32, 10000, Zagreb, Croatia. npavin@phy.hr.engJournal ArticleResearch Support, Non-U.S. Gov't20180903

EnglandNat Commun1015285552041-17230KIF11 protein, humanEC 3.6.4.4KinesinsIMCell Line, TumorHeLa CellsHumansKinesinsgeneticsKinetochoresphysiologyultrastructureMicroscopy, ConfocalMicrotubulesphysiologyultrastructureModels, TheoreticalSpindle ApparatusgeneticsphysiologyultrastructureTorqueThe authors declare no competing interests.20182152018862018956020189560201912560201893epublish30177685PMC612095710.1038/s41467-018-06005-710.1038/s41467-018-06005-7Prosser SL, Pelletier L. Mitotic spindle assembly in animal cells: a fine balancing act. Nat. Rev. Mol. Cell Biol. 2017;18:187–201. doi: 10.1038/nrm.2016.162.10.1038/nrm.2016.16228174430McIntosh JR, Molodtsov MI, Ataullakhanov FI. Biophysics of mitosis. Q. Rev. Biophys. 2012;45:147–207. doi: 10.1017/S0033583512000017.10.1017/S0033583512000017PMC443317122321376Musacchio, A. & Desai, A. A molecular view of kinetochore assembly and function. Biology(Basel)6, 10.3390/biology6010005 (2017).PMC537199828125021Pavin N, Tolić IM. 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