Cell and nuclear volume regulation: phase separation of chromatin in nucleus

Living cells regulate their volume using a diverse set of mechanisms, to maintain their structural and functional integrity. Experiments on adhered cells surprisingly revealed that their volume is significantly reduced as their basal area is increased [1]. We have formulated a physical theory [2] which includes the effects of both electrostatics and cell activity on ion transport to predict a generic relation for how adhered cells regulate their volume in response to changes in their area, in agreement with the observations. Those measurements also show that the nuclear volume scales with the cell volume. Recently, the Volk group [3] using intact-organism imaging, discovered that changes in nuclear volume dramatically varies the spatial organization of chromatin (DNA and associated proteins); this may have important consequences for gene expression. A simple polymeric model [4] that includes the competition of chromatin self-attraction and interactions with the nuclear membrane, predicts transitions in the chromatin organization relative to the nucleus from peripheral to central to conventional, as the nuclear volume is reduced, as measured in the experiments of the Volk group.

References:
1. Experiments: Weitz group (Harvard); Jian group (Hefei); Piel group (Curie)
2. Theory: R. Adar (TAU and Curie)
3. Experiments: D. Amiad-Pavlov, D. Lorber, T. Volk – Dept. Molecular Genetics, WIS
4. Theory: G. Bajpai, O. Arana Adame, D. Deviri – Dept. Chemical and Biological Physics, WIS

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