A Transient-Network Model of Condensate Aging and Morphology Transition in Phase Separation
Abstract
Biomolecular condensates can undergo striking changes, such as transitioning from a liquid-like to a gel- or a solid-like aggregate due to changes in molecular interactions in response to changes in the biochemical environment. The question of how modified molecular interactions lead to such a transition in the material properties and spatial organization of condensates has not yet been elucidated. To address this question, we represent the biochemical environment as a triphasic mixture comprising a liquid-like protein-rich phase, a network-like protein-rich phase, and solvent. Owing to a change in the biochemical environment, protein molecules can reversibly switch between two conformational states. In a switched conformational state, the cross-linking domains of molecules are exposed which promote transient network formation in phase separated states. We develop a transient-network model and a continuum framework that couples phase separation, molecular switching, and dynamic cross-linking to predict condensate morphology and mechanics. The transient-network model predicts that a non-aging network behaves like a Maxwell fluid. When a network slowly ages via stabilization of cross-links, it shows Maxwell-like behavior and waiting time-dependent relaxation. However, a strongly aged network shows elastic recoil like characteristic of a Kelvin-Voigt solid. Our coupled continuum model demonstrates that the interplay of molecular switching and dynamic cross-linking in network formation shapes the spatial organization of condensate phases. In summary, this work demonstrates a mechanistic route explaining how conformational switching and molecular cross-linking regulate material properties and morphology of condensates.
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BibTeX
@misc{debnath2026transientnetwork,
title = {{A Transient-Network Model of Condensate Aging and Morphology Transition in Phase Separation}},
author = {Bhanjan Debnath},
howpublished = {arXiv},
year = {2026},
month = nov,
doi = {10.48550/arxiv.2608.23076},
eprint = {2608.23076},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2608.23076},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - UNPB
TI - A Transient-Network Model of Condensate Aging and Morphology Transition in Phase Separation
AU - Bhanjan Debnath
PY - 2026
DA - 2026/11/04
PB - arXiv
DO - 10.48550/arxiv.2608.23076
UR - https://arxiv.org/abs/2608.23076
AB - Biomolecular condensates can undergo striking changes, such as transitioning from a liquid-like to a gel- or a solid-like aggregate due to changes in molecular interactions in response to changes in the biochemical environment. The question of how modified molecular interactions lead to such a transition in the material properties and spatial organization of condensates has not yet been elucidated. To address this question, we represent the biochemical environment as a triphasic mixture comprising a liquid-like protein-rich phase, a network-like protein-rich phase, and solvent. Owing to a change in the biochemical environment, protein molecules can reversibly switch between two conformational states. In a switched conformational state, the cross-linking domains of molecules are exposed which promote transient network formation in phase separated states. We develop a transient-network model and a continuum framework that couples phase separation, molecular switching, and dynamic cross-linking to predict condensate morphology and mechanics. The transient-network model predicts that a non-aging network behaves like a Maxwell fluid. When a network slowly ages via stabilization of cross-links, it shows Maxwell-like behavior and waiting time-dependent relaxation. However, a strongly aged network shows elastic recoil like characteristic of a Kelvin-Voigt solid. Our coupled continuum model demonstrates that the interplay of molecular switching and dynamic cross-linking in network formation shapes the spatial organization of condensate phases. In summary, this work demonstrates a mechanistic route explaining how conformational switching and molecular cross-linking regulate material properties and morphology of condensates.
ER -