Role of paclitaxel on critical nucleation concentration of tubulin and its effects thereof

Abstract

Paclitaxel is an anticancer drug that stabilizes microtubules by suppressing their dynamic instability. It binds to the lumen of the microtubules and enhances subunit interaction. In the present work, we show that the critical concentration of tubulins required to polymerize microtubules follows an inverse power law relation with the amount of paclitaxel added during polymerization. With an increase in paclitaxel concentration from 0.1 μM to 10 μM, the critical nucleation concentration decreases by 89%. We propose stabilization of microtubule nuclei in the presence of taxol for this observation. In addition, lowering in the critical nucleation concentration left fewer tubulins for growth, which resulted in shorter microtubules. Addition of 10 μM taxol resulted in reduced steady state length of microtubules by 37.5%. These observations are explained based on microtubule nuclei stabilization and subsequent depletion of tubulin pool. We also show mathematically, that taxol reduces the rate constant of shortening more prominently (by 100 folds), compared to the rate constant of elongation.

Keywords: Microtubule; Nucleation; Paclitaxel.