Osmotic Coupling of Mechanics and Epigenetics Regulates Chromatin Phase Organization
Abstract
Cells experience epigenetic, osmotic, and mechanical perturbations that reorganize chromatin, yet how these distinct cues are integrated into a common physical response of the nucleus remains unclear. Here, we identify nuclear hydration as a central state variable that links microenvironmental perturbations to chromatin phase organization and nuclear mechanics. We develop a non-equilibrium mesoscale model that couples chromatin elasticity, water transport, and epigenetic reaction-diffusion kinetics. In this framework, chromatin behaves as a deformable polymer that segregates into coexisting water-rich euchromatic and water-poor heterochromatic phases, whose compositions and morphologies are regulated by hydration-dependent swelling, elastic strain, and histone-mark interconversion. The model predicts that epigenetic perturbations, osmotic shocks, and volume-changing mechanical loads reorganize chromatin by shifting intranuclear water content, nuclear volume, and euchromatin-heterochromatin phase balance. It further predicts that anisotropic forces impose directional strain, driving heterochromatin elongation, alignment, and lamellar transitions. Quantitative comparisons with super-resolution imaging, AFM and chromatin-accessibility measurement - across pharmacological, osmotic, and mechanical perturbations including confinement and micropatterning - support these predictions. Together, our results establish a chemo-mechano-osmotic framework in which nuclear hydration integrates biochemical and biophysical cues to regulate chromatin organization across scales.
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BibTeX
@misc{kant2026osmotic,
title = {{Osmotic Coupling of Mechanics and Epigenetics Regulates Chromatin Phase Organization}},
author = {Aayush Kant and Monika Dhankhar and Rohit Joshi and Zixian Guo and Vinayak Vinayak and Diana I. Cruz and Kedi Wang and Ivan V. Surovtsev and Megan King and Abhijit Majumder and Jung-Hwan Lee and Hae-Won Kim and Elizabeth Hinde and Guilherme PF Nader and Vivek B. Shenoy},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762828},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762828v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Osmotic Coupling of Mechanics and Epigenetics Regulates Chromatin Phase Organization
AU - Aayush Kant
AU - Monika Dhankhar
AU - Rohit Joshi
AU - Zixian Guo
AU - Vinayak Vinayak
AU - Diana I. Cruz
AU - Kedi Wang
AU - Ivan V. Surovtsev
AU - Megan King
AU - Abhijit Majumder
AU - Jung-Hwan Lee
AU - Hae-Won Kim
AU - Elizabeth Hinde
AU - Guilherme PF Nader
AU - Vivek B. Shenoy
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762828
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762828v1
AB - Cells experience epigenetic, osmotic, and mechanical perturbations that reorganize chromatin, yet how these distinct cues are integrated into a common physical response of the nucleus remains unclear. Here, we identify nuclear hydration as a central state variable that links microenvironmental perturbations to chromatin phase organization and nuclear mechanics. We develop a non-equilibrium mesoscale model that couples chromatin elasticity, water transport, and epigenetic reaction-diffusion kinetics. In this framework, chromatin behaves as a deformable polymer that segregates into coexisting water-rich euchromatic and water-poor heterochromatic phases, whose compositions and morphologies are regulated by hydration-dependent swelling, elastic strain, and histone-mark interconversion. The model predicts that epigenetic perturbations, osmotic shocks, and volume-changing mechanical loads reorganize chromatin by shifting intranuclear water content, nuclear volume, and euchromatin-heterochromatin phase balance. It further predicts that anisotropic forces impose directional strain, driving heterochromatin elongation, alignment, and lamellar transitions. Quantitative comparisons with super-resolution imaging, AFM and chromatin-accessibility measurement - across pharmacological, osmotic, and mechanical perturbations including confinement and micropatterning - support these predictions. Together, our results establish a chemo-mechano-osmotic framework in which nuclear hydration integrates biochemical and biophysical cues to regulate chromatin organization across scales.
SN - 2692-8205
ER -