The mitotic spindle is an important intermediate structure in eucaryotic 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. It is widely believed that the spindle starts forming by the `capture' of chromosome pairs, held together by kinetochores, by randomly searching microtubules. We present a complete analytical formulation of this problem, in the case of a single fixed target and for arbitrary cell size. We derive a set of Green's functions for the microtubule dynamics and an associated set of first passage quantities. An implicit analytical expression for the probability distribution of the search time is then obtained , with appropriate boundary conditions at the outer cell membrane. We extract the conditions of optimized search from our formalism. Our results are in qualitative and semi-quantitative agreement with known experimental results for different cell types{\it   .
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 .
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eucaryotic
eukaryotic
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It is widely believed that the spindle starts forming by
Several mechanisms are at work towards the formation of the spindle, one of which is
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We present a complete analytical formulation of this problem, in the case of a single fixed target and for arbitrary cell size. We derive a set of Green's functions for the microtubule dynamics and an associated set of first passage quantities. An implicit analytical expression for the probability distribution of the search time is then obtained , with appropriate boundary conditions at the outer cell membrane. We extract the conditions of optimized search from our formalism. Our results are in qualitative and semi-quantitative agreement with known experimental results for different cell types
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
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Xenopus
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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