The role of microtubule assembly dynamics in mitotic force generation and functional organization of living cells.

This article summarizes the author's presentation at the Baylor Medical School Symposium on the Biophysics of Microtubules, held April 12 to 14, 1996, in Houston, Texas. It presents a brief historical sketch and discusses the role that assembly/disassembly of microtubules is likely to be playing in force generation for chromosome movement and related organellar positioning in living cells. The article starts out with how polarized light microscopy of living cells had laid the foundation for this concept in the 1950s and 1960s, but was then eclipsed for some 2 decades following the discovery of force generation by microtubule sliding powered by an ATP-hydrolyzing motor protein, dynein. The intriguing recent discoveries: that microtubules undergo dynamic instability; that they both assemble and disassemble right at the kinetochore where they are attached to the chromosome; and that assembling and disassembling microtubules can of themselves push and pull reasonable loads in model experiments, even in the absence of hydrolyzable nucleotides, have refocused serious attention on the probable role played by assembly/disassembly of microtubules. This mode of force generation may well be intricately coupled, and interact, with force-generating and/or dynamic attachment roles played by "motor" proteins, especially at the kinetochore.