Congrats, this is really cool! I already tried it on one of my favorite tomos and the result looks fantastic.

Great work! So cool to see how far the field has already advanced in just a few years.

The software acts as a computational shortcut to denser sampling, which is often not feasible due to radiation damage limits. → Better angular sampling, sharper segmentation, improved particle localization.

Thank you, Michaela!

Thanks!

Finally, we selected a representative fragment of chromatin, modelled it including histone tails, and performed all-atom MD simulations on it. The simulation showed an overall stable molecular arrangement with H4 tails mediating a stacking interaction.

Examining the 3D heterochromatin organization, we found a 37 nm edge-to-edge distance between connected nucleosomes and two trinucleosome arrangements: a smaller stacked population and a larger one with longer nucleosome distances, suggesting no strict long-range order for native heterochromatin.

We then used a physics-based model to predict DNA linkers between the nucleosomes obtained by cryo-ET. This allowed us to visualize kbp-long chromatin fragments from inside human cells.

Meta-analysis on the nucleosome coordinates revealed dense chromatin patches with local concentrations exceeding 200 mg/mL and showed native chromatin behaves like an intermediate between liquid and gas with some short-range order.

Thanks to these high-confidence peaks, we obtained the highest-resolved in situ chromatosome structure to date (with no interpolation). With local resolutions of core histones near 6Å, we confirmed the secondary structures reported in numerous in vitro studies. #TeamTomo

First, we enhanced template matching for nucleosomes by generating interpolated tilts between existing ones to reconstruct higher-contrast tomograms. Check out www.biorxiv.org/content/10.1... for method details. #TeamTomo

We investigated the molecular architecture of heterochromatin using cryo-ET (#TeamTomo) with enhanced template matching, subtomogram averaging, DNA linker predictions, and MD simulations.