Scientists capture the most detailed 3D views yet of DNA droplets that organize cells

Scientists from UT Southwestern, UC San Diego, the University of Cambridge, and HHMI’s Janelia Research Campus have produced the most detailed 3D images to date of synthetic chromatin condensates—droplet-like structures formed by nucleosomes that mimic how DNA compacts inside cells. Using cryo-electron tomography (cryo-ET), which involves flash-freezing samples, slicing them into ultra-thin sections, and imaging from multiple angles, the team reconstructed near-native 3D views of chromatin fibers and nucleosomes within these condensates. Their analysis revealed that the length of linker DNA between nucleosomes critically influences how chromatin fibers organize and phase-separate, explaining variations in condensate properties and shedding light on the physical basis of DNA compaction. Importantly, the synthetic condensates closely resemble native chromatin organization inside cells, linking molecular structures to the macroscopic behavior of these membrane-less droplets. This breakthrough provides a framework for understanding how chromatin and other biomolecular condensates