Jcb_201612064 1525..1532

1525 The Rockefeller University Press $30.00 J. Cell Biol. Vol. 216 No. 6 1525–1531 https://doi.org/10.1083/jcb.201612064 Introduction During eukaryotic cell division, the mitotic spindle mediates the separation of chromosomes into the two daughter cells (Gadde and Heald, 2004; Kapoor, 2017). Microtubules within the spindle are organized in a dense array, with their positions, orientations, lengths, regions of overlap, and nucleation sites regulated by motor and nonmotor proteins. During the division process, mechanical forces are necessary to separate the chromosomes, as demonstrated by the pioneering work of Nicklas et al. (1982). Using glass microneedles to directly interact with the chromosomes of dividing grasshopper spermatocytes, the researchers showed that chromosomes in anaphase can experience significant forces. Although calculations based on the observed size and speed of micron-sized chromosomes moving through a viscous environment suggest that it would require only ∼0.1 pN of force to move chromosomes, Nicklas showed that the spindle machinery is capable of exerting forces of up to 700 pN before chromosome motion was stalled (Nicklas, 1983, 1988). This value is many hundreds of times larger than the maximum force typically generated by a single motor protein. This remarkable result suggests that the spindle can produce significantly more mechanical work by exerting forces on the micron-length scale than is minimally required to move chromosomes. However, the results from this series of experiments also give rise to an important question: If large forces on chromosomes are being applied from the center of the bipolar spindle outward, toward the poles, how does a spindle maintain its structural integrity and not simply collapse under this tension? One plausible answer is that the network of microtubules that fill the spindle but do not interact directly with kinetochores are generating opposing forces, resulting in a force balance across the whole of the bipolar spindle network. These forces could allow the spindle to operate in a steady state, maintaining its structural integrity but also allowing for chromosome motions through the dense microtubule network. Here, we highlight findings from recent studies that are likely to be important for spindle organization and function, including overlap length–dependent pushing and braking forces, protein friction and autonomous clustering of protein ensembles by frictional asymmetry, and entropic forces generated by diffusible cross-linkers. Together, these findings point toward the development of a more refined map of forces in the spindle and will motivate cell biological experiments that directly test these mechanical principles.