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Spatial Regulation Improves Antiparallel Microtubule Overlap during Mitotic Spindle Assembly

Wilbur E. Channels ^*, François J. Nédélec , Yixian Zheng  and Pablo A. Iglesias ^*

^* Department of Electrical and Computer Engineering, The Johns Hopkins University, Baltimore, Maryland; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg D-69117, Germany; and Department of Embryology, Carnegie Institution of Washington and Howard Hughes Medical Institute, Baltimore, Maryland

Correspondence: Address reprint requests to Pablo A. Iglesias, Department of Electrical and Computer Engineering, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218. E-mail: pi{at}jhu.edu.

The mitotic spindle plays an essential role in chromosome segregation during cell division. Spindle formation and proper function require that microtubules with opposite polarity overlap and interact. Previous computational simulations have demonstrated that these antiparallel interactions could be created by complexes combining plus- and minus-end-directed motors. The resulting spindles, however, exhibit sparse antiparallel microtubule overlap with motor complexes linking only a nominal number of antiparallel microtubules. Here we investigate the role that spatial differences in the regulation of microtubule interactions can have on spindle morphology. We show that the spatial regulation of microtubule catastrophe parameters can lead to significantly better spindle morphology and spindles with greater antiparallel MT overlap. We also demonstrate that antiparallel microtubule overlap can be increased by having new microtubules nucleated along the length of existing astral microtubules, but this increase negatively affects spindle morphology. Finally, we show that limiting the diffusion of motor complexes within the spindle region increases antiparallel microtubule interaction.