Abstract
SummaryThe forces which orient the spindle in human cells remain poorly understood due to a lack of direct mechanical measurements in mammalian systems. We use magnetic tweezers to measure the force on human mitotic spindles. Combining the spindle’s measured resistance to rotation, the speed it rotates after laser ablating astral microtubules, and estimates of the number of ablated microtubules reveals that each microtubule contacting the cell cortex is subject to ∼1 pN of pulling force, suggesting that each is pulled on by an individual dynein motor. We find that the concentration of dynein at the cell cortex and extent of dynein clustering are key determinants of the spindle’s resistance to rotation, with little contribution from cytoplasmic viscosity, which we explain using a biophysically based mathematical model. This work reveals how pulling forces on astral microtubules determine the mechanics of spindle orientation and demonstrates the central role of cortical dynein clustering.HighlightsCytoplasmic viscosity does not determine the spindle’s resistance to rotationEach astral microtubule that contacts the cell cortex is pulled on by a single dynein motorPulling forces on astral microtubules determine the mechanics of spindle orientationThe mechanics of spindle orientation is regulated by clustering of dynein motors at the cell cortexGraphical Abstract
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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