title: Physical determinants of bipolar mitotic spindle assembly and stability in fission yeast.
abstract: Mitotic spindles use an elegant bipolar architecture to segregate duplicated chromosomes with high fidelity. Bipolar spindles form from a monopolar initial condition; this is the most fundamental construction problem that the spindle must solve. Microtubules, motors, and cross-linkers are important for bipolarity, but the mechanisms necessary and sufficient for spindle assembly remain unknown. We describe a physical model that exhibits de novo bipolar spindle formation. We began with physical properties of fission-yeast spindle pole body size and microtubule number, kinesin-5 motors, kinesin-14 motors, and passive cross-linkers. Our model results agree quantitatively with our experiments in fission yeast, thereby establishing a minimal system with which to interrogate collective self-assembly. By varying the features of our model, we identify a set of functions essential for the generation and stability of spindle bipolarity. When kinesin-5 motors are present, their bidirectionality is essential, but spindles can form in the presence of passive cross-linkers alone. We also identify characteristic failed states of spindle assembly-the persistent monopole, X spindle, separated asters, and short spindle, which are avoided by the creation and maintenance of antiparallel microtubule overlaps. Our model can guide the identification of new, multifaceted strategies to induce mitotic catastrophes; these would constitute novel strategies for cancer chemotherapy.
authors.affiliation: Department of Physics, University of Colorado, Boulder, CO 80309, USA.; PULS Group, Department of Physics and Cluster of Excellence: Engineering of Advanced Materials, Friedrich-Alexander University Erlangen-Nurnberg, Nagelsbachstr. 49b, Erlangen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Blackwell
authors.affiliation: Department of Physics, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Christopher
authors.identifier: 0000-0002-3673-1310
authors.initials: C
authors.lastname: Edelmaier
authors.affiliation: Department of Physics, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Oliver
authors.identifier: 0000-0001-5216-0290
authors.initials: O
authors.lastname: Sweezy-Schindler
authors.affiliation: Department of Physics, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Adam
authors.identifier: 0000-0003-2616-2801
authors.initials: A
authors.lastname: Lamson
authors.affiliation: Department of Physics, University of Colorado, Boulder, CO 80309, USA.; Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Zachary R
authors.identifier: 0000-0002-0322-0717
authors.initials: ZR
authors.lastname: Gergely
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Eileen
authors.identifier: 0000-0001-6053-3077
authors.initials: E
authors.lastname: O'Toole
authors.affiliation: Department of Physics, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Ammon
authors.initials: A
authors.lastname: Crapo
authors.affiliation: Department of Physics, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Loren E
authors.identifier: 0000-0002-1104-0126
authors.initials: LE
authors.lastname: Hough
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: J Richard
authors.identifier: 0000-0002-7165-9748
authors.initials: JR
authors.lastname: McIntosh
authors.affiliation: Department of Physics, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Matthew A
authors.identifier: 0000-0002-8366-5598
authors.initials: MA
authors.lastname: Glaser
authors.affiliation: Department of Physics, University of Colorado, Boulder, CO 80309, USA.; Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Meredith D
authors.initials: MD
authors.lastname: Betterton
mesh_terms: D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*
chemical_list: D029702:Schizosaccharomyces pombe Proteins; D016547:Kinesins