Chromatin phase separation and nuclear shape fluctuations are correlated in a polymer model of the nucleus

Autor: Ali Goktug Attar, Jaroslaw Paturej, Edward J. Banigan, Aykut Erbaş
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nucleus, Vol 15, Iss 1 (2024)
Druh dokumentu: article
ISSN: 19491034
1949-1042
1949-1034
DOI: 10.1080/19491034.2024.2351957
Popis: Abnormal cell nuclear shapes are hallmarks of diseases, including progeria, muscular dystrophy, and many cancers. Experiments have shown that disruption of heterochromatin and increases in euchromatin lead to nuclear deformations, such as blebs and ruptures. However, the physical mechanisms through which chromatin governs nuclear shape are poorly understood. To investigate how heterochromatin and euchromatin might govern nuclear morphology, we studied chromatin microphase separation in a composite coarse-grained polymer and elastic shell simulation model. By varying chromatin density, heterochromatin composition, and heterochromatin-lamina interactions, we show how the chromatin phase organization may perturb nuclear shape. Increasing chromatin density stabilizes the lamina against large fluctuations. However, increasing heterochromatin levels or heterochromatin-lamina interactions enhances nuclear shape fluctuations by a “wetting”-like interaction. In contrast, fluctuations are insensitive to heterochromatin’s internal structure. Our simulations suggest that peripheral heterochromatin accumulation could perturb nuclear morphology, while nuclear shape stabilization likely occurs through mechanisms other than chromatin microphase organization.
Databáze: Directory of Open Access Journals
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