A Compliant Molecular Clutch Model for Kinetochore<br/><br/>Motion Driven By Microtubule Disassembly

Thursday, May 16, 2013 - 10:15am - 11:05am
Keller 3-180
David Odde (University of Minnesota, Twin Cities)
Kinetochores are nano-structures that mechanically couple chromosomes
to dynamic microtubules to generate the forces necessary for proper
chromosome segregation during mitosis. Recent studies reveal new
details of the kinetochore’s molecular composition and structure,
demonstrating the mechanically compliant nature of the kinetochore
linkage to the microtubule. This finding stands in contrast to
previous theoretical models of kinetochore motility (Hill, 1985;
Molodtsov et al., 2005), which assumed an infinitely stiff linkage.
Here, we present a compliant kinetochore-clutch model where an array
of compliant linkers (“clutches”) interacts reversibly with a dynamic
microtubule tip. We explore the behavior of a kinetochore-clutch
system with various clutch parameters including: (1) clutch affinity
for the MT-lattice, (2) clutch stiffness, (3) preference for tubulin
intra-/interdimer association, (4) diffusion rate, and (5) tensional
load force. We find that clutch stiffness is critical in governing
the distribution of linkers over the MT tip, and thus in turn,
modulating microtubule tip dynamics. Surprisingly, clutch affinity
for the MT-lattice can be varied over a wide range with minimal effect
on system behavior. We also find that clutch diffusion on the MT
lattice is not critical for kinetochore coupling. Finally, we find
that tensional load force shifts the distribution of linkers toward
the MT tip to directly suppress net disassembly and prime MTs for
rescue. Together, our theoretical studies predict a potentially
important role for clutch mechanical compliance in kinetochore
motility and control of microtubule assembly-disassembly.
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