Shimamoto, Y., Maeda, Y.T., Ishiwata, S., Libchaber, A.J., Kapoor, T.M. (2011) Insights into the micromechanical properties of the metaphase spindle. Cell, 145, 1062-74. (Highlighted in Cell PaperFlick; Current Biology, 21(18), R688-R690)
The metaphase spindle must generate nanonewton-scale forces to pull chromosomes apart and must also be robust to withstand opposing forces of equal magnitude. Forces also act on the metaphase spindle to control its position and size. In addition, chromosomes, which are proportionately large cargoes, must be allowed to move through the spindle’s dense cytoskeletal polymer network. The forces associated with these chromosome motions exert deformations within the metaphase spindle. How this essential cellular structure maintains functional fidelity and structural stability in the face of these forces that can vary in magnitude, orientation and time-scales is poorly understood. To address this question we measured the orientation- and timescale-dependent micromechanical properties of the metaphase spindle. For this analysis we designed a dual force-calibrated microneedle-based system. As the metaphase spindle is unstable in buffer and cannot be assembled with purified proteins, we used spindles assembled in Xenopus egg extracts. We uncovered for the first time the viscoelastic properties of the metaphase spindle. Our findings help explain how this essential structure transmits forces and how it accommodates proportionately large deformations. We show that the metaphase spindle responds either more solid-like or liquid-like depending on the rates at which forces are applied. For example, at the rates of chromosome movement, the spindle is most liquid-like and can dissipate strain due to local deformations while maintaining overall structural integrity. For fast-acting forces, such as those that control position, the spindle is more solid-like and moves without deformation. We propose a simple mechanical model that accounts for these viscoelastic properties and can link them to spindle microtubules and crosslinking proteins. It is likely that our findings for the metaphase spindle will also shed new light on how other similar polymer networks, such as microtubules needed for directional transport in neurons, assemble and carry out force-generating functions.
The metaphase spindle must generate nanonewton-scale forces to pull chromosomes apart and must also be robust to withstand opposing forces of equal magnitude. Forces also act on the metaphase spindle to control its position and size. In addition, chromosomes, which are proportionately large cargoes, must be allowed to move through the spindle’s dense cytoskeletal polymer network. The forces associated with these chromosome motions exert deformations within the metaphase spindle. How this essential cellular structure maintains functional fidelity and structural stability in the face of these forces that can vary in magnitude, orientation and time-scales is poorly understood. To address this question we measured the orientation- and timescale-dependent micromechanical properties of the metaphase spindle. For this analysis we designed a dual force-calibrated microneedle-based system. As the metaphase spindle is unstable in buffer and cannot be assembled with purified proteins, we used spindles assembled in Xenopus egg extracts. We uncovered for the first time the viscoelastic properties of the metaphase spindle. Our findings help explain how this essential structure transmits forces and how it accommodates proportionately large deformations. We show that the metaphase spindle responds either more solid-like or liquid-like depending on the rates at which forces are applied. For example, at the rates of chromosome movement, the spindle is most liquid-like and can dissipate strain due to local deformations while maintaining overall structural integrity. For fast-acting forces, such as those that control position, the spindle is more solid-like and moves without deformation. We propose a simple mechanical model that accounts for these viscoelastic properties and can link them to spindle microtubules and crosslinking proteins. It is likely that our findings for the metaphase spindle will also shed new light on how other similar polymer networks, such as microtubules needed for directional transport in neurons, assemble and carry out force-generating functions.
