Polymer Physics Predicts Conformational Diversity of Individual Chromatin Molecules
- 1Dipartimento di Ingegneria Chimica dei Materiali e della Produzione Industriale (DICMaPi), Università di Napoli Federico II, Piazzale Vincenzo Tecchio 80, 80125 Naples, Italy
- 2INFN Napoli, Complesso Universitario di Monte Sant’Angelo, 80126 Naples, Italy
- 3Dipartimento di Fisica, Università di Napoli Federico II, Complesso Universitario di Monte Sant’Angelo, 80126 Naples, Italy
Abstract
Recent advances in single-cell and super-resolution imaging have revealed that chromatin adopts highly heterogeneous and dynamic three-dimensional conformations across individual cells. However, the extent of this variability, its underlying mechanisms, and its functional consequences remain difficult to quantify experimentally. Here, we review recent progress in combining polymer physics, molecular dynamics simulations, and data-driven approaches to reconstruct and predict ensembles of three-dimensional chromatin conformations at the single-molecule level. We discuss how polymer phase-separation and loop-extrusion models can reproduce both population-averaged contact data and independent single-cell imaging measurements. These approaches help disentangle different sources of conformational diversity, including the intrinsic thermodynamic degeneracy of polymer folding and cell-to-cell heterogeneity. We further discuss how perturbation of key architectural factors, particularly cohesin, affects chromatin conformation and single-cell structural variability. Overall, polymer-physics models provide a quantitative framework to connect molecular mechanisms underlying chromatin folding with the heterogeneous conformational ensembles observed experimentally in individual molecules.
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BibTeX
@article{pierno2026polymer,
title = {{Polymer Physics Predicts Conformational Diversity of Individual Chromatin Molecules}},
author = {Florinda Di Pierno and Ciro Di Carluccio and Matteo Olimpo and Gabriele Marotta and Mario Nicodemi and Mattia Conte},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31213870},
url = {https://www.mdpi.com/1420-3049/31/21/3870},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Polymer Physics Predicts Conformational Diversity of Individual Chromatin Molecules
AU - Florinda Di Pierno
AU - Ciro Di Carluccio
AU - Matteo Olimpo
AU - Gabriele Marotta
AU - Mario Nicodemi
AU - Mattia Conte
PY - 2026
DA - 2026/10/27
JO - Molecules
DO - 10.3390/molecules31213870
UR - https://www.mdpi.com/1420-3049/31/21/3870
AB - Recent advances in single-cell and super-resolution imaging have revealed that chromatin adopts highly heterogeneous and dynamic three-dimensional conformations across individual cells. However, the extent of this variability, its underlying mechanisms, and its functional consequences remain difficult to quantify experimentally. Here, we review recent progress in combining polymer physics, molecular dynamics simulations, and data-driven approaches to reconstruct and predict ensembles of three-dimensional chromatin conformations at the single-molecule level. We discuss how polymer phase-separation and loop-extrusion models can reproduce both population-averaged contact data and independent single-cell imaging measurements. These approaches help disentangle different sources of conformational diversity, including the intrinsic thermodynamic degeneracy of polymer folding and cell-to-cell heterogeneity. We further discuss how perturbation of key architectural factors, particularly cohesin, affects chromatin conformation and single-cell structural variability. Overall, polymer-physics models provide a quantitative framework to connect molecular mechanisms underlying chromatin folding with the heterogeneous conformational ensembles observed experimentally in individual molecules.
SN - 1420-3049
ER -