Understanding microtubule dynamics: The synergy of technology, theory, and experiment

This perspective traces the ways in which information obtained with different technologies for sample preparation, imaging, and image analysis has interacted with biochemical information and theories of protein polymerization to form an ever deeper understanding of microtubule dynamics. Essential to this progress has been a more accurate knowledge of microtubule structure, especially at the polymer's tip, where subunits are commonly added and removed. I follow the contributions of light microscopy, i.e., bright-field, polarization, differential interference contrast, and dark-field optics, then fluorescence microscopy with either immunolabeling or fluorescent labeling of tubulin itself. I also trace electron microscopy from its use on thin sections of fixed materials through negative staining of isolated polymers, then on to imaging of fast-frozen samples with cryo-electron microscopy and tomography. The results from these observations are combined with data from biochemistry and x-ray crystallography, image analysis, and atomistic molecular dynamic modeling to build what is likely to be an accurate overview of how microtubules polymerize.