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Team #9530Page 2 of 6TitileSummaryDuring cell division, mitotic spindles are assembled by microtubule-based motor proteins1, 2. The bipolar organization of spindles is essential for proper segregation of chromosomes, and requires plus-end-directed homotetrameric motor proteins of the widely conserved kinesin-5 (BimC) family3. Hypotheses for bipolar spindle formation include the pushpull mitotic muscle model, in which kinesin-5 and opposing motor proteins act between overlapping microtubules2, 4, 5. However, the precise roles of kinesin-5 during this process are unknown. Here we show that the vertebrate kinesin-5 Eg5 drives the sliding of microtubules depending on their relative orientation. We found in controlled in vitro assays that Eg5 has the remarkable capability of simultaneously moving at 20 nm s-1 towards the plus-ends of each of the two microtubules it crosslinks. For anti-parallel microtubules, this results in relative sliding at 40 nm s-1, comparable to spindle pole separation rates in vivo6. Furthermore, we found that Eg5 can tether microtubule plus-ends, suggesting an additional microtubule-binding mode for Eg5. Our results demonstrate how members of the kinesin-5 family are likely to function in mitosis, pushing apart interpolar microtubules as well as recruiting microtubules into bundles that are subsequently polarized by relative sliding. We anticipate our assay to be a starting point for more sophisticated in vitro models of mitotic spindles. For example, the individual and combined action of multiple mitotic motors could be tested, including minus-end-directed motors opposing Eg5 motility. Furthermore, Eg5 inhibition is a major target of anti-cancer drug development, and a well-defined and quantitative assay for motor function will be relevant for such developmentsContentTitile1Summary11Introduction11.1Restatement of the Problem11.2Background11.1.1Common Solving Technique11.1.2Previous Works11.3Example12Analysis of the Problem12.1Outline of the Approach12.2Basic Assumptions12.3Definitions and Key Terms13Calculating and Simplifying the Model14The Model Results15Validating the Model16Strengths and Weaknesses16.1Strengths16.2Weaknesses17Food for Thought18Conclusion1References1Appendices1Appendix A Source Code1Appendix B1Team #9530Page 4 of 61 Introduction1.1 Restatement of the Problem1.2 Background1.1.1 Common Solving Technique1.1.2 Previous Works1.3 Example2 Analysis of the Problem2.1 Outline of the Approach2.2 Basic Assumptionslllll2.3 Definitions and Key TermsllllTable 1.SymbolMeaningUnit3 Calculating and Simplifying the Model4 The Model Results5 Validating the Model6 Strengths and Weaknesses6.1 Strengthsllll6.2 Weaknessesllll7 Food for Thought8 Conclusion.ReferencesAppen
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