Emergent domain segregation in self-interacting polymers explains chromosome 3D conformations in single human cells
Phys. Rev. E 113, 054416 – Published 28 May, 2026
DOI: https://doi.org/10.1103/g6k5-nkbd
Abstract
Polymer physics models have been employed to elucidate the 3D organization of chromosomes in the cell nucleus. However, how well they capture chromatin architectures at the single-molecule level remains poorly understood. Here, we consider a minimal polymer model where folding is driven by sequence-specific self-interactions between cognate monomer types, leading to their separation into spatially segregated globular domains. Focusing on a key genomic region in human IMR90 cells, we demonstrate that the model accurately reproduces the distribution of individual chromatin conformations as validated by single-cell super-resolution microscopy experiments. The structural variability across cells is naturally explained by the predicted thermodynamic ensemble of domain-segregated states, hence providing a robust validation of the model basic ingredients with no additional molecular parameters.
