Nuclear Mechanics and Stem Cell Differentiation

Mao, Xinjian; Gavara, Núria; Song, Guanbin

doi:10.1007/s12015-015-9610-z

Cited by 18 publications

(13 citation statements)

References 60 publications

(140 reference statements)

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“…It has been suggested that chromatin density might itself act to regulate gene expression in a stem-cell population [65]. While the embryonic stem-cell state has a chromatin organization that is best described as a highly correlated fluid, the differentiated state fluctuates far less, with condensed heterochromatin foci forming during the differentiation of pluripotent embryonic stem cells [66]. The formation of heterochromatin domains has recently been argued to be mediated by phase separation [39,40].…”

Section: Discussionmentioning

confidence: 99%

Chromatin Compaction, Auxeticity, and the Epigenetic Landscape of Stem Cells

Tripathi

Menon

2019

Phys. Rev. X

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When embryonic stem cells differentiate, the mechanical properties of their nuclei evolve en route to their terminal state. Measurements of the deformability of cell nuclei in the transitional state that intervenes between the embryonic stem-cell state and the differentiation primed state of mouse stem cells indicate that such nuclei are auxetic; i.e., they have a negative Poisson's ratio. We show, using a theoretical model, how this remarkable mechanical behavior results from the coupling between chromatin compaction states and nuclear shape. Our biophysical approach, which treats chromatin as an active polymer system whose mechanics is modulated by nucleosome binding and unbinding, reproduces experimental results. It provides testable predictions for changes in chromatin compaction as a function of applied force, for the correlations of chromatin compaction and nuclear shape, and for the in-phase and out-of-phase response of these quantities to an applied uniaxial oscillatory force. Our model yields a biophysical interpretation of the epigenetic landscape of stem cells, also suggesting how this landscape might be probed experimentally.

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Section: Discussionmentioning

confidence: 99%

Chromatin Compaction, Auxeticity, and the Epigenetic Landscape of Stem Cells

Tripathi

Menon

2019

Phys. Rev. X

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“…The mechanical behaviour of the nucleus and its role in cellular mechanotransduction depends on multiple factors, including its own makeup and that of its environment. Intrinsically, the expression of laminA/C (type V intermediate filaments) and the organization of chromatin are believed to determine the mechanical properties of the nucleus 1 . Externally, cytoskeletal networks, notably actin, have also been suggested to play a key role in nuclear state and mechanics 2 .…”

Section: Introductionmentioning

confidence: 99%

Actomyosin and vimentin cytoskeletal networks regulate nuclear shape, mechanics and chromatin organization

Keeling

Flores

Dodhy

et al. 2017

Sci Rep

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The regulation of nuclear state by the cytoskeleton is an important part of cellular function. Actomyosin stress fibres, microtubules and intermediate filaments have distinct and complementary roles in integrating the nucleus into its environment and influencing its mechanical state. However, the interconnectedness of cytoskeletal networks makes it difficult to dissect their individual effects on the nucleus. We use simple image analysis approaches to characterize nuclear state, estimating nuclear volume, Poisson’s ratio, apparent elastic modulus and chromatin condensation. By combining them with cytoskeletal quantification, we assess how cytoskeletal organization regulates nuclear state. We report for a number of cell types that nuclei display auxetic properties. Furthermore, stress fibres and intermediate filaments modulate the mechanical properties of the nucleus and also chromatin condensation. Conversely, nuclear volume and its gross morphology are regulated by intracellular outward pulling forces exerted by myosin. The modulation exerted by the cytoskeleton onto the nucleus results in changes that are of similar magnitude to those observed when the nucleus is altered intrinsically, inducing chromatin decondensation or cell differentiation. Our approach allows pinpointing the contribution of distinct cytoskeletal proteins to nuclear mechanical state in physio- and pathological conditions, furthering our understanding of a key aspect of cellular behaviour.

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“…While the embryonic stem call state has a chromatin organization that is best described as a highly correlated fluid, the differentiated state fluctuates far less, with condensed heterochromatin foci forming during the differentiation of pluripotent embryonic stem cells (Mao et al, 2015). The formation of heterochromatin domains has recently been argued to be mediated by phase separation (Larson et al, 2017;Strom et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Chromatin compaction states, nuclear shape fluctuations and auxeticity: A biophysical interpretation of the epigenetic landscape of stem cells

Tripathi¹,

Menon²

2018

Preprint

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When embryonic stem cells differentiate, the mechanical properties of their nuclei evolve en route to their terminal state. Measurements of the deformability of cell nuclei in the transitional state that intervenes between the embryonic stem cell state and the differentiation primed state of mouse stem cells, indicate that such nuclei are auxetic i.e. have a negative Poisson's ratio. We show, using a theoretical model, how this unusual mechanical behaviour results from the coupling between chromatin compaction states and nuclear shape. Our biophysical approach, which treats chromatin as an active polymer system whose mechanics is modulated by nucleosome binding and unbinding, reproduces experimental results while providing new predictions. We discuss ways of testing these predictions. Our model suggests a biophysical interpretation of the epigenetic landscape of stem cells.Keywords: mechanical properties of stem cells, auxetic behaviour, epigenetic landscape, stem cell biophysics Correspondence: menon@imsc.res.in Highlights • A mathematical model describes the coupling of chromatin compaction states with fluctuations in the shape of stem cell nuclei • It explains the observation of auxetic behaviour in mouse stem cells in the transitional state • The results agree with experiments and the model provides several testable predictions • These results suggest a biophysical interpretation of Waddington's epigenetic landscape in terms of chromatin compaction states

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Nuclear Mechanics and Stem Cell Differentiation

Cited by 18 publications

References 60 publications

Chromatin Compaction, Auxeticity, and the Epigenetic Landscape of Stem Cells

Chromatin Compaction, Auxeticity, and the Epigenetic Landscape of Stem Cells

Actomyosin and vimentin cytoskeletal networks regulate nuclear shape, mechanics and chromatin organization

Chromatin compaction states, nuclear shape fluctuations and auxeticity: A biophysical interpretation of the epigenetic landscape of stem cells

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