A computational model for the formation of lamin-B mitotic spindle envelope and matrix.

Recent reports show that, after nuclear envelope breakdown, lamin-B, a component of the nuclear lamina in interphase, localizes around the mitotic spindle as a membranous network. How this process occurs, however, and how it influences mitotic spindle morphogenesis is unclear. Here, we develop a computational model based on a continuum description to represent the abundance and location of various molecular species involved during mitosis, and use the model to test a number of hypotheses regarding the formation of the mitotic matrix. Our model illustrates that freely diffusible nuclear proteins can be captured and transported to the spindle poles by minus-end-directed microtubule (MT) motors. Moreover, simulations show that these proteins can be used to build a shell-like region that envelopes the mitotic spindle, which helps to improve the focusing of the mitotic spindle by spatially restricting MT polymerization and limiting the effective diffusion of the free MTs. Simulations also confirm that spatially dependent regulation of the spindle network through the Ran system improves spindle focusing and morphology. Our results agree with experimental observations that lamin-B reorganizes around the spindle and helps to maintain spindle morphology.

Spatial regulation improves antiparallel microtubule overlap during mitotic spindle assembly.

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.