Interplay Between Spindle Architecture and Function - International Review of Cell and Molecular Biology - page 114

assembly remain to be established, given the long polymeric nature of these
molecules, it is possible that they can function to stabilize or confine spindle
components ( Fig. 3.8 D). Understanding the architectural and structural fea-
tures of these different spindles and the different force requirements for
chromosome segregation by comparative analysis will be necessary to deter-
mine whether confinement or structural support is necessary for the function
of the spindle and whether this comes from the nuclear envelope or poly-
meric meshworks of macromolecules.
5.4. Simulations of microtubule arrangement in the spindle
Despite the significant insights stemming from years of experiments on spin-
dle structure, the detailed underlying architectures of most spindles are yet to
be determined. This is primarily due to the technical challenge of imaging a
densely packed structure made up of bundled MT polymers by either elec-
tron microscopy or light microscopy. Recently, to gain insight into arrange-
ments of MTs compatible with the organizational properties and defined
steady-state structure of the spindle, several computational models have been
developed. While many models have provided quantitative insight into spe-
cific parts of spindle form or functions, such as the dynamics of individual
MTs and rates of spindle length changes, two complementary spindle sim-
ulation studies are most related to spindle architecture.
Both simulations were designed to understand the complex interactions,
forces, and structures that emerge from many factors acting in concert.
Though the fundamental implementations were different, these simulations
used combinations of MTs and various motor proteins or regulatory activ-
ities to elucidate how the basic features of the spindle, such as antiparallel
arrays and spindle poles, might be attained ( Fig. 3.9 ). Many different simpli-
fications were used to minimize computational complexity and study differ-
ent aspects of spindle architecture, yet the two simulations found
qualitatively similar results. In each case, a sliding motor (modeled after
kinesin-5 proteins) driving outward sliding of MTs and a clustering force
were necessary to form the bipolar MT array and spindle poles. In the sim-
ulation of Burbank et al. (2007) , clustering was produced by a motor that
bound to two MTs and walked toward their minus-ends, modeled after
dynein ( Fig. 3.9 A). In the simulation by Loughlin et al. (2010) , clustering
was introduced through an activity that was transported to the minus-end
of MTs and could cross-link within 5 m m from the end but did not apply
a force, modeled after NuMA ( Fig. 3.9 B). In both models, MT nucleation