Videos

A Compliant Molecular Clutch Model for Kinetochore Motion Driven By Microtubule Disassembly

Presenter
May 16, 2013
Keywords:
  • Molecular
MSC:
  • 92C40
Abstract
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.