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Mechanochemical Model of Microtubule Structure and Self-Assembly Kinetics

Vincent VanBuren ^*, Lynne Cassimeris ^* and David J. Odde 

^* Lehigh University, Department of Biological Sciences, Bethlehem, Pennsylvania; and University of Minnesota, Department of Biomedical Engineering, Minneapolis, Minneapolis

Correspondence: Address reprint requests to David J. Odde, Tel.: 612-624-9618; E-mail: odde{at}mail.ahc.umn.edu.

Microtubule self-assembly is largely governed by the chemical kinetics and thermodynamics of tubulin-tubulin interactions. An important aspect of microtubule assembly is that hydrolysis of the ß-tubulin-associated GTP promotes protofilament curling. Protofilament curling presumably drives the transition from tip structures associated with growth (sheetlike projections and blunt ends) to those associated with shortening (rams' horns and frayed ends), and transitions between these structures have been proposed to be important for growth-shortening transitions. However, previous models for microtubule dynamic instability have not considered such structures or mechanics explicitly. Here we present a three-dimensional model that explicitly incorporates mechanical stress and strain within the microtubule lattice. First, we found that the model recapitulates three-dimensional tip structures and rates of assembly and disassembly for microtubules grown under standard conditions, and we propose that taxol may stabilize microtubule growth by reducing flexural rigidity. Second, in contrast to recent suggestions, it was determined that sheetlike tips are more likely to undergo catastrophe than blunt tips. Third, partial uncapping of the tubulin-GTP cap provides a possible mechanism for microtubule pause events. Finally, simulations of the binding and structural effects of XMAP215 produced the experimentally observed growth and shortening rates, and tip structure.

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