The SCALE Science Lunch Seminar continues on Wednesday, July 8, 2026, at 12:30 h (s.t.) with a talk by Stefanie Redemann Ph.D. (School of Medicine, University of Virginia).
From textbook cartoons to in situ reality: rethinking spindle architecture through large-scale electron tomography and cryo-ET
How cells build a bipolar spindle to segregate chromosomes is a fundamental question in cell biology, yet our view of spindle architecture has long rested on models inferred from light microscopy and early electron microscopy that lacked the resolution to visualize individual microtubules within the intact cell. Using large-scale 3D electron tomography of plastic-embedded C. elegans embryos and human cells, we first challenged the classical pole-centric model by demonstrating that spindle microtubules are short and discontinuous, a fundamentally different picture than the long, continuous fibers depicted in textbooks. Moving to cryo-electron tomography of intact, vitrified human RPE-1 cells revealed an even more unexpected organization. Spindle microtubules arrange into locally antiparallel bundles with a strikingly consistent 8 nm wall-to-wall spacing, which is too narrow for molecular motors to crosslink adjacent filaments directly. Instead, spacing scales inversely with local microtubule density, pointing to density-driven steric interactions analogous to liquid crystal ordering as a key organizational principle. Motor perturbation experiments show that the kinesin-5 Eg5 locally generates antiparallel overlap independently of spindle bipolarity, while dynein regulates microtubule density to maintain overall architecture. Together, these findings support a bottom-up, self-organized model of spindle assembly driven by steric forces and local motor activity. Beyond the specific biology, this work illustrates how advances in in situ structural biology, from large-scale plastic-section tomography to cryo-ET of whole cells, are not merely improving resolution, but fundamentally changing what we think we know about cellular machines.
The SCALE Science Lunch Seminar will take place in hybrid format. We warmly invite you to join us in person at the MPI for Biophysics, where a light lunch and coffee will be provided after the seminar. The talk will also be streamed live via Zoom. The zoom link will be sent by e-mail to the SCALE mailing list. To subscribe to the mailing list, please send an e-mail to scale-office@uni-frankfurt.de.
We look forward to welcoming you to the next SCALE Science Lunch Seminar.
