Structural effects of cap, crack, and intrinsic curvature on the microtubule catastrophe kinetics.
The Journal of chemical physics
American Institute of Physics
MetadataShow full item record
Lee, C., & Terentjev, E. (2019). Structural effects of cap, crack, and intrinsic curvature on the microtubule catastrophe kinetics.. The Journal of chemical physics, 151 (13), 135101. https://doi.org/10.1063/1.5122304
Microtubule (MT) experience an effect called `catastrophe', which is the transition from the MT growth to a sudden dramatic shrinkage in length. The straight GTP-tubulin cap at the lament tip, and the intrinsic curvature of GDP-tubulins are known to be the key thermodynamic factors that determine MT catastrophe, while the hydrolysis of this GTP-cap acts as the kinetic control of the process. Although several theoretical models have been developed, assuming the catastrophe occurs when the GTP-cap shrinks to a minimal stabilizing size, the structural effect of the GTP-cap and GDP-curvature was not explicitly included, thus their influence on catastrophe kinetics remains less understood. To investigate this structural effect, we apply a single-protofi lament model with one GTP-cap while assuming a random hydrolysis mechanism, and take the occurrence of a crack in the lateral bonds between neighboring protofi laments as the onset of the catastrophe. Therein, we fi nd the effective potential of the tip along the peel-off direction, and formulate the catastrophe kinetics as a mean fi rst-passage time problem, subject to thermal fluctuations. We consider cases with and without a compressive force on the MT tip, both of which give a quadratic effective potential, making MT catastrophe an Ornstein-Uhlenbeck process in our formalism. In the free-standing case, the mean catastrophe time has a sensitive tubulin-concentration dependence, similar to a double-exponential function, and agrees well with experiment. For a compressed MT, we fi nd a modfi ed exponential function of force that shortens the catastrophe time.
Embargo Lift Date
External DOI: https://doi.org/10.1063/1.5122304
This record's URL: https://www.repository.cam.ac.uk/handle/1810/296839
All rights reserved