The instability of stabilization

Actin filaments and microtubules control the shape of cells and organize their contents. The proteins that form these cytoskeletal polymers were identified and isolated decades ago—actin in 1942 (1) and tubulin in 1968 (2)—but we still argue about some of their basic properties. New work from Niedermayer et al. (3), however, puts us on the right track, or more properly back on the right track, to understanding how actin filaments fall apart. After years of study, how is it still possible for otherwise reasonable people to disagree about how actin filaments and microtubules assemble and disassemble? The shortest answer I can think of has two parts: (i) the details matter, and (ii) the experiments are hard. The details matter because small differences in the rate, mechanism, or geometry of polymer assembly and disassembly produce cytoskeletal networks with different architectures. Ultimately, we want to understand how cells manipulate such basic biochemical properties to produce different cytoskeletal structures with different biological functions. How, for example, does one cell construct a 3D pseudopod that pushes forward the plasma membrane; a linear stress fiber that pulls on cell adhesions; and a contractile ring that splits the cell in two—all from actin filaments? The experiments are hard, in part, because cytoskeletal polymers are constructed from large numbers of weak, noncovalent interactions, and they are dynamic, sometimes even ephemeral structures. To study assembly and disassembly of cytoskeletal polymers, we require techniques that maintain their native structure: techniques that often push technical boundaries in both biochemistry and physics. It is not surprising then, that the work of Niedermayer et al. represents the joint effort of two groups, one led by biochemist Marie France Carlier and the other by physicist Rheinhard Lipowsky. The first single-polymer studies of cytoskeletal systems relied on static samples, often imaged by electron microscopy. …