Contribution of Dynamic Instability to Microtubule Organization
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Date
2008
Authors
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Publisher
University of  Manitoba
Abstract
Microtubules  are  hollow  cylindrical protein  structures  found  in  all eukaryotic cells,  and
essential  in  several  cellular processes,  including  cell  motility,  cell  division,  vesicle  trafficking  and  maintenance  of cell shape.  The  building block  of microtubtles,  tubulin,  is  one
of  the  proven targets  for  anticancer  drugs.  A microtubule  exhibits  a remarkable  property, termed  dynam,i.c  i,nstabi,Ii.ty,  in  which  it  is  able  to  switch  stochastically between  two
distinct  states. In  one  state,  the  microtubule  grows while  in  the  other,  it  shrinks.  The
balance between  the  growing  and  shrinking states  is  crucial  for  the normal functioning  of
the  cell. One  of the interesting  questions  that  cell biologists  have pondered over  the  years
is:  what is  the  biological function  of  dynamic  instability?  While  some great strides  have
been  made in  answering this  question,  the details  of the  precise  nature of  the  mechanism
of dynamic  instability  in  relation  to  their  roles  are  not well  understood. In  this  thesis
some  biologically  pìausible  mathematical  modeìs  for  microtubule  dynamics 'in  ui,tro are
developed.  Two  of the  models  are  developed with  the  exclusion  of dynamic  insiability
while the  others are  with  its  inclusion.  Aiso  considered  are  two  different  modes of nucleation of microtubules:  saturating  and  non-saturating mode. The models are analyzed
and numerical  simulations  conducted, with  an  aim of  mathematically  assessing  the  role  of
dynamic  instability  in  the  integral  microtubule  dynamics  i,n  ui,tro.  Results  indicate  that
dynamic instability  induces  the  formation  of  microtubules  from  the tubuÌin  subunits,  and
that  dynamic  instability  depends  on the  GTP-tubulin  concentration
Description
A Thesis/Practicum  submitted  to  the  Faculty  of Graduate  Studies  of The  University of
Manitoba in  partial  fulfillment  of the  requirement  of the  degree
of Master of Science
Keywords
Microtubule Organization