A MOLECULAR-MECHANICAL MODEL OF MICROTUBULE

¹ University of CO, Boulder, USA
² Semenov Institute of Chemical Physics, Moscow, Russia
³ Institute of mathematical problems of biology, Pushchino, Russia
⁴ Natl. Res. Cntr. Hematology

^* To whom correspondence should be addressed. E-mail: fazly{at}hc.comcor.ru.

Submitted on August 23, 2004
Revised on October 7, 2004
Accepted on 9 February 2005

	Abstract

Dynamic instability of microtubules is thought to be regulated by biochemical transformations within tubulin dimers that are coupled to the hydrolysis of bound GTP. Structural studies of nucleotide-bound tubulin dimers have recently provided a concrete basis for understanding how these transformations may contribute to microtubule dynamic instability. To analyze these ideas we have developed a molecular-mechanical model in which structural and biochemical properties of tubulin are used to predict the shape and stability of microtubules. From simple and explicit features of tubulin we define bond energy relationships and explore the impact of their variations on integral microtubule properties. This modeling provides quantitative predictions about the GTP-cap. It specifies important mechanical features underlying microtubule instability and shows that this property does not require GTP-hydrolysis to alter the strength of tubulin-tubulin bonds. The plus microtubule end is stabilized by at least two layers of GTP-tubulin subunits, while the minus end requires at least one; this and other differences between the ends are explained by asymmetric force balances. Overall, this model provides a new link between the biophysical characteristics of tubulin and the physiological behavior of microtubules. It will also be useful in building a more complete description of microtubule dynamics and mechanics.

Key Words: GTP-cap, dynamic instability, mathematical model, microtubule end, tubulin

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