1. A First-Passage-Time Theory for Search and Capture of Chromosomes by Microtubules in Mitosis
- Author
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Bindu S. Govindan and Manoj Gopalakrishnan
- Subjects
Quantitative Biology - Subcellular Processes ,Xenopus ,General Mathematics ,Immunology ,Mitosis ,FOS: Physical sciences ,Spindle Apparatus ,Biology ,Microtubules ,Models, Biological ,Quantitative Biology - Quantitative Methods ,Chromosomes ,General Biochemistry, Genetics and Molecular Biology ,Spindle pole body ,Animals ,animal ,biological model ,cell cycle ,centromere ,chromosome ,mammal ,mathematical phenomena ,microtubule ,mitosis ,mitosis spindle ,physiology ,Saccharomycetales ,Cell Cycle ,Kinetochores ,Mammals ,Mathematical Concepts ,Mitotic Spindle Apparatus ,Eukaryota ,Mammalia ,Physics - Biological Physics ,Subcellular Processes (q-bio.SC) ,Condensed Matter - Statistical Mechanics ,Quantitative Methods (q-bio.QM) ,General Environmental Science ,Microtubule nucleation ,Pharmacology ,Statistical Mechanics (cond-mat.stat-mech) ,General Neuroscience ,Microtubule organizing center ,Cell biology ,Computational Theory and Mathematics ,Biological Physics (physics.bio-ph) ,Mitotic exit ,FOS: Biological sciences ,Premature chromosome condensation ,General Agricultural and Biological Sciences ,Astral microtubules ,Cytokinesis - Abstract
The mitotic spindle is an important intermediate structure in eukaryotic cell division, in which each of a pair of duplicated chromosomes is attached through microtubules to centrosomal bodies located close to the two poles of the dividing cell. Several mechanisms are at work towards the formation of the spindle, one of which is the `capture' of chromosome pairs, held together by kinetochores, by randomly searching microtubules. Although the entire cell cycle can be up to 24 hours long, the mitotic phase typically takes only less than an hour. How does the cell keep the duration of mitosis within this limit? Previous theoretical studies have suggested that the chromosome search and capture is optimized by tuning the microtubule dynamic parameters to minimize the search time. In this paper, we examine this conjecture. We compute the mean search time for a single target by microtubules from a single nucleating site, using a systematic and rigorous theoretical approach, for arbitrary kinetic parameters. The result is extended to multiple targets and nucleating sites by physical arguments. Estimates of mitotic time scales are then obtained for different cells using experimental data. In yeast and mammalian cells, the observed changes in microtubule kinetics between interphase and mitosis are beneficial in reducing the search time. In {\it Xenopus} extracts, by contrast, the opposite effect is observed, in agreement with the current understanding that large cells use additional mechanisms to regulate the duration of the mitotic phase., Comment: Significant changes in the text and figures and new material added, version to appear in Bull. Math. Biol
- Published
- 2011
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