Abstract:
Microtubules (MTs) and MT associated proteins form an essential component of the
eukaryotic cytoskeleton. Asters are radial arrays of MTs, involved in vital cellular
processes such as spindle assembly,chromosome segregation, intracellular transport,
cell motility and organelle positioning. While several studies have addressed mechanisms
for movement and positioning of a single or a pair of asters, only a few
studies report the mechanical basis of multi aster positioning. Understanding how
their numbers and position is mechanically regulated is the focus of this study. Using
computational models, I have studied the mechanical basis of multiple-asters in
confinement. In order to determine the general principles of multi-aster behaviour,
the MT-motor parameter space was extensively explored and the key findings are
discussed in the thesis.
The multi-aster centering in meiotic oocytes of mouse was recapitulated in a minimal
model of dynein gradient, coupling dyneins, MT dynamics and cortical pushing.
This suggests motor gradient as a mechanism for directed motility of small asters
in large cells. While segregated arrangement of asters emerged with a hexagonal
dominance, in presence of kinesin-5 motors and stabilized MTs at optimal system
size. A similar hexagon ordering observed in ascidian meiotic oocytes, validated the
simulation results. On cortical localization of dyneins, dynamic asters self-organized
into collective rotational motion. This suggests possible mechanisms that may have
evolved to suppress such motions in vivo. To explicitly simulate cortical dyneins,
yeast dynein was modeled and the motor number dependent MT transport statistics
was comparable to the MT gliding experiments.
The combined a↵ect of MTs, motors and system size on mult-aster motility and
position is demonstrated. This study provides a framework for theoretical understanding
of the principles of multi-aster mechanics in spindle assembly, sub-cellular
organization and embryogenesis
