Molecular Horizons Seminar - Dr Benjamin Dalton

The mitotic spindle is a highly dynamic, bipolar structure that emerges from the self-organisation of microtubules, molecular motors, and other proteins. Activity, generated by molecular motors, drives steady-state microtubule fluxes throughout the spindle structure, which are essential for the correct bipolar spindle architecture. However, until recently it was not understood how the local activity of molecular motors could enable coherent spindle-scale microtubule flows and organisation. In a recent paper [1], we showed that a gelation transition enables long-range microtubule transport, causing a spindle to self-organise into two oppositely-polarised microtubule gels, which are driven apart by kinesin motors at the spindle mid-plane, hence generating characteristic poleward flows. By combining laser ablation experiments on Xenopus Laevis egg extract spindles with detailed computer simulations of active filament networks, we showed that microtubule gels undergoing rapid polymerisation turnover can exhibit long stress-relaxation times and propagate stresses over long distances. We also showed that in the presence of branching microtubule nucleation, either reducing activity or decreasing network connectivity results in the formation of an inverted bipolar spindle architecture, which we confirm with both experiment and simulation. Overall, we reveal an unexpected connection between rheology and architecture in bipolar spindle self-organisation.

[1] Dalton, B.A., Oriola, D., Decker, F. et al. Nat. Phys. 18, 323–331 (2022)