Microtubule dynamic instability: some possible physical mechanisms and their implications.
Video microscopic observation of a population of microtubules at steady state of assembly shows individual microtubules which interconvert between phases of growing and shrinking. The average duration of either phase is strongly affected by the tubulin concentration. Close to the steady-state (or 'critical') concentration, the mean excursion lengths may be of cellular dimensions, suggesting that dynamic instability can function as a control mechanism for the spatial organization of microtubule arrays. Numerical modelling, based on a limited number of assumptions, illustrates the transition behaviour, and the polar nature of this instability. The basic concept is that tubulin-GTP adds to a terminal position of the microtubule lattice and causes hydrolysis of the tubulin-GTP at a previously terminal lattice position [1, 2]. The predictions of this model can be evaluated experimentally. Further, examination of the consequences of introducing into the lattice a molecule such as a tubulin-drug complex, with altered capacity for helical propagation, provides a quantitative model for substoichiometric inhibition of microtubule dynamics and growth. This principle could have a more general relevance to mechanisms of regulation of microtubules within the cytoskeleton.
Bayley
P M
PM
Division of Physical Biochemistry, National Institute for Medical Research, Mill Hill, London, U.K.
Martin
S R
SR
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008954:Models, Biological; D014404:Tubulin / Q000378:metabolism
D000970:Antineoplastic Agents; D014404:Tubulin; D006160:Guanosine Triphosphate