Abstract
Microtubules are highly dynamic polymers that play fundamental roles in all eukaryotes. As the control of microtubule nucleation and regulation is central to their function, there has long been interest in obtaining quantitative descriptions of microtubule polymerization. Textbooks have focused on variations of a nucleation-elongation mechanism: monomers are in rapid equilibrium with an unstable oligomer (nucleus), but once the nucleus forms, the polymer grows by monomer addition. While such mechanisms readily capture the actin assembly process, they are inadequate to describe the physical mechanism by which the much larger and more complex microtubules assemble. Here we develop a new model for microtubule self-assembly that has three key features: i) microtubules initiate via the formation of closed, 2D sheet-like structures which grow faster the larger they become; ii) the dominant pathway proceeds via addition of complete longitudinal or lateral layers; iii) as predicted by structural studies and the lattice model, the formation of lateral interactions requires payment of an energetic penalty for straightening early structures. This model quantitatively fits experimental assembly data, and provides important insights into biochemical determinants and assembly pathways for microtubule nucleation.
