Structural effects of cap, crack, and intrinsic curvature on the microtubule catastrophe kinetics.

Abstract

Microtubules (MTs) experience an effect called "catastrophe," which is the transition from the MT growth to a sudden dramatic shrinkage in length. The straight guanosine triphosphate (GTP)-tubulin cap at the filament tip and the intrinsic curvature of guanosine diphosphate (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 is not explicitly included; thus, their influence on catastrophe kinetics remains less understood. To investigate this structural effect, we apply a single-protofilament model with one GTP-cap while assuming a random hydrolysis mechanism and take the occurrence of a crack in the lateral bonds between neighboring protofilaments as the onset of the catastrophe. Therein, we find the effective potential of the tip along the peel-off direction and formulate the catastrophe kinetics as a mean first-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 the experiment. For a compressed MT, we find a modified exponential function of force that shortens the catastrophe time.