Mitotic spindle is a complex molecular machine segregating
chromosomes
before cell division. While experiments have revealed the basic
mechanisms of spindle
dynamics, a complete picture of how molecular motor forces are
integrated in mitosis
is still lacking. In this study we undertook systemic analysis to
identify potential mechanisms
of force integration that will reproduce spindle development in
Drosophila embryo. First,
computer assembled millions of different models based on various
possible combinations
of molecular motors. Mathematically, each model is a system of ~ 20 ODEs
and algebraic
equations characterized by ~ 50 parameters. Then, searches in the 'model
space' based on repeated stochastic
optimization using genetic algorithms followed by cluster analysis
identified distinct strategies for
force integration. Our searches identified 1450 distinct groups of
models that can reproduce
experimentally observed pole separation in wild type embryo but only 21
distinct strategies
that can reproduce pole separation in both wild type and eight different
mutant or biochemically
inhibited embryos. Furthermore, out of these 21 plausible models only
one is supported by
additional data on chromosome motility. In addition, analysis of
different force balance strategies r
evealed general design principles that are common among all plausible
models.