The late 1970s brought the discovery that nonionic detergents such as Triton X-100 could extract most cell components and leave behind the insoluble cytoskeleton. “Just making cytoskeletons and naming them was brand new,” recalls John Heuser (Washington University in St. Louis, MO). He credits the efforts of James Spudich, Susan Brown, and Klaus Weber for perfecting the structure's isolation.
But the favored EM technique at the time—involving thin sectioning of samples embedded in plastic—was nearly impossible with the gossamer skeletons. And air-drying for negative staining caused them to collapse into a two-dimensional jumble. So Heuser tried a new approach: freeze-drying samples in a vacuum, where the solid water would just evaporate straight to the gas phase, thus removing the surface tension of air-drying.
“Good freeze-drying just requires good, rapid freezing with little time for ice crystals to form,” Heuser explains. He had already perfected the...