Confined Polymers in a Poor Solvent: The Role of Bonding to the Surface

Adame-Arana, Omar; Safran, S. A.

doi:10.1021/acs.macromol.1c00343

Cited by 7 publications

(5 citation statements)

References 36 publications

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“…For example, self-attraction can lead to chromatin collapse (as in refs. 23 and 24 ). Since we are interested in identifying the dominant forces, we estimate an upper bound on the possible values of R g and subsequently on the pressures p p .…”

Section: Forces Involved In Nuclear Volume Determinationmentioning

confidence: 99%

Balance of osmotic pressures determines the nuclear-to-cytoplasmic volume ratio of the cell

Deviri

Safran

2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance For over a century, it has been known that the ratio of the nuclear and cytoplasm volumes (NC ratio), rather than the separate volumes, is constant among cells of many types of organisms. Changes of the NC ratio are associated with cancerous transformations, suggesting that the ratio has physiological importance. Notably, the dominant regulatory mechanism of the NC ratio has not been identified. Here, we use physical estimates of the forces implicated in nuclear volume determination and show that they are dominated by the osmotic pressure of actively transported proteins. Inspired by this, we formulate a minimal model for the cytoplasmic and nuclear volumes that predicts the NC ratio and the factors that modulate it, in agreement with published experiments.

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Section: Forces Involved In Nuclear Volume Determinationmentioning

confidence: 99%

Balance of osmotic pressures determines the nuclear-to-cytoplasmic volume ratio of the cell

Deviri

Safran

2022

Proc. Natl. Acad. Sci. U.S.A.

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“…For simplicity we consider the case where both types of monomers have the same molecular size

. Motivated by recent experimental and theoretical studies on chromatin organization showing that chromatin behaves as a self-attractive polymer (polymer in poor solvent) ( Amiad-Pavlov et al, 2021 ; Bajpai et al, 2021 ; Adame-Arana and Safran, 2021 ), we model both blocks (in the absence of chromatin-binding protein complexes) as being in poor solvent conditions; both blocks phase separate from the aqueous phase, consistent with the experiments. However, due to the difference in attraction of AA vs. BB, the two types of blocks will undergo a further, microphase separation, reminiscent of the data in Amiad-Pavlov et al, 2021 , where acetylated chromatin is mostly found surrounding regions of higher density of chromatin.…”

Section: Resultsmentioning

confidence: 65%

Regulation of chromatin microphase separation by binding of protein complexes

Adame-Arana

Bajpai

Lorber

et al. 2023

eLife

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We show evidence of the association of RNA polymerase II (RNAP) with chromatin in a core-shell organization, reminiscent of microphase separation where the cores comprise dense chromatin and the shell, RNAP and chromatin with low density. These observations motivate our physical model for the regulation of core-shell chromatin organization. Here, we model chromatin as a multiblock copolymer, comprising active and inactive regions (blocks) that are both in poor solvent and tend to be condensed in the absence of binding proteins. However, we show that the solvent quality for the active regions of chromatin can be regulated by the binding of protein complexes (e.g., RNAP and transcription factors). Using the theory of polymer brushes, we find that such binding leads to swelling of the active chromatin regions which in turn modifies the spatial organization of the inactive regions. In addition, we use simulations to study spherical chromatin micelles, whose cores comprise inactive regions and shells comprise active regions and bound protein complexes. In spherical micelles the swelling increases the number of inactive cores and controls their size. Thus, genetic modifications affecting the binding strength of chromatin-binding protein complexes may modulate the solvent quality experienced by chromatin and regulate the physical organization of the genome.

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“…For simplicity we consider the case where both types of monomers have the same molecular size a. Motivated by recent experimental and theoretical studies on chromatin organization showing that chromatin behaves as a self-attractive polymer (polymer in poor solvent) [19,22,51], we model both blocks (in the absence of chromatin-binding protein complexes) as being in poor solvent conditions; both blocks phase separate from the aqueous phase, consistent with the experiments. However, due to the difference in attraction of AA vs. BB, the two types of blocks will undergo a further, microphase separation, reminiscent of the data in [19], where acetylated chromatin is mostly found surrounding regions of higher density of chromatin.…”

Section: B Theoretical Model: Chromatin As a Multiblock Copolymermentioning

confidence: 89%

Regulation of chromatin microphase separation by adsorbed protein complexes

Adame-Arana

Bajpai

Lorber

et al. 2022

Preprint

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We show evidence of the association of RNA Polymerase II (RNAP) with chromatin in a core-shell organization, reminiscent of microphase separation where the cores comprise dense chromatin and the shell, RNAP and chromatin with low density. These observations motivate our physical model for the regulation of core-shell chromatin organization. Here, we model chromatin as a multiblock copolymer, comprising active and inactive regions (blocks) that are both in poor solvent and tend to be condensed in the absence of binding proteins. However, we show that the solvent quality for the active regions of chromatin can be regulated by the binding of protein complexes (e.g. RNAP). Using the theory of polymer brushes, we find that such binding leads to swelling of the active chromatin regions which in turn, modifies the spatial organization of the inactive regions. In addition, we use simulations to study spherical chromatin micelles, whose cores comprise inactive regions and shells comprise active regions and bound protein complexes. In spherical micelles the swelling increases the number of inactive cores and controls their size. Thus, genetic modifications affecting the binding strength of chromatin-binding protein complexes may modulate the solvent quality experienced by chromatin and regulate the physical organization of the genome.

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Confined Polymers in a Poor Solvent: The Role of Bonding to the Surface

Cited by 7 publications

References 36 publications

Balance of osmotic pressures determines the nuclear-to-cytoplasmic volume ratio of the cell

Balance of osmotic pressures determines the nuclear-to-cytoplasmic volume ratio of the cell

Regulation of chromatin microphase separation by binding of protein complexes

Regulation of chromatin microphase separation by adsorbed protein complexes

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