Contributions of Microtubule Dynamic Instability and Rotational Diffusion to Kinetochore Capture.
Microtubule dynamic instability allows search and capture of kinetochores during spindle formation, an important process for accurate chromosome segregation during cell division. Recent work has found that microtubule rotational diffusion about minus-end attachment points contributes to kinetochore capture in fission yeast, but the relative contributions of dynamic instability and rotational diffusion are not well understood. We have developed a biophysical model of kinetochore capture in small fission-yeast nuclei using hybrid Brownian dynamics/kinetic Monte Carlo simulation techniques. With this model, we have studied the importance of dynamic instability and microtubule rotational diffusion for kinetochore capture, both to the lateral surface of a microtubule and at or near its end. Over a range of biologically relevant parameters, microtubule rotational diffusion decreased capture time, but made a relatively small contribution compared to dynamic instability. At most, rotational diffusion reduced capture time by 25%. Our results suggest that while microtubule rotational diffusion can speed up kinetochore capture, it is unlikely to be the dominant physical mechanism for typical conditions in fission yeast. In addition, we found that when microtubules undergo dynamic instability, lateral captures predominate even in the absence of rotational diffusion. Counterintuitively, adding rotational diffusion to a dynamic microtubule increases the probability of end-on capture.
Department of Physics, University of Colorado, Boulder, Colorado.
Robert
R
Blackwell
Department of Physics, University of Colorado, Boulder, Colorado.
Oliver
O
Sweezy-Schindler
Department of Physics, University of Colorado, Boulder, Colorado.
Christopher
C
Edelmaier
Department of Physics, University of Colorado, Boulder, Colorado; Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado.
Zachary R
ZR
Gergely
Department of Physics, University of Colorado, Boulder, Colorado.
Patrick J
PJ
Flynn
Department of Physics, University of Colorado, Boulder, Colorado.
Salvador
S
Montes
Department of Physics, University of Colorado, Boulder, Colorado.
Ammon
A
Crapo
Department of Aerospace Engineering Sciences, University of Colorado, Boulder, Colorado.
Alireza
A
Doostan
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado.
J Richard
JR
McIntosh
Department of Physics, University of Colorado, Boulder, Colorado.
Matthew A
MA
Glaser
Department of Physics, University of Colorado, Boulder, Colorado; Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado. Electronic address: mdb@colorado.edu.
Meredith D
MD
Betterton
D004058:Diffusion; D007700:Kinetics; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D009010:Monte Carlo Method; D012399:Rotation; D012568:Schizosaccharomyces / Q000166:cytology
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