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Universal Properties and Phase Transitions in Chromatin Dynamics.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Universal Properties and Phase Transitions in Chromatin Dynamics./
作者:
Eshghi, Iraj.
面頁冊數:
1 online resource (296 pages)
附註:
Source: Dissertations Abstracts International, Volume: 85-01, Section: B.
Contained By:
Dissertations Abstracts International85-01B.
標題:
Physics. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30315454click for full text (PQDT)
ISBN:
9798379775452
Universal Properties and Phase Transitions in Chromatin Dynamics.
Eshghi, Iraj.
Universal Properties and Phase Transitions in Chromatin Dynamics.
- 1 online resource (296 pages)
Source: Dissertations Abstracts International, Volume: 85-01, Section: B.
Thesis (Ph.D.)--New York University, 2023.
Includes bibliographical references
In the nucleus of each living cell resides its genome, which contains the information necessary for the cell to function and reproduce. This takes a polymeric form known as chromatin, organized in a complex hierarchical structure compacted within the cell nucleus. Chromatin is organized and behaves differently depending on the cell type in question, while maintaining certain fundamental structural properties. This polymer is subject to a variety of active processes such as DNA repair, transcription, and replication, driving both its organization and dynamics far from thermodynamic equilibrium. Therefore beyond its biological significance, chromatin is interesting from a physical perspective as it is an example of an active polymer system sustained in an out-of-equilibrium state. Therefore, the study of chromatin dynamics can be enlightening both for the study of active materials as well as basic biological science.In this thesis, we investigate which dynamical properties of chromatin are universal among different types of cells. Furthermore, we seek to identify the physical nature of the transitions between the different dynamical states of chromatin. Once these have been identified, we seek to develop a physical model which can capture these universal properties. In Chapter 4, we study the changes in chromatin material properties upon cell differentiation. We show that chromatin undergoes a local sol-gel transition when the cell differentiates from a stem cell to a neuron. This transition is characterized by a significant changes in the chromatin compaction profile, along with corresponding changes in both local and global dynamics.We begin by studying the dynamics of chromatin in five different cell lines, and seek to identify which dynamical and material properties are shared among them. We find that the chromatin in all five cell lines forms coherent regions at long times, the size of which is set by the size of the cell nuclei. The viscoelastic moduli of the chromatin in the differentiated cell lines are the same up to rescaling time by their relaxation time, and rescaling viscosity by heterochromatin fraction.We then develop a theoretical framework to underpin this observation of universality. We begin by considering the possible types of activity that could act on a two-fluid system such as chromatin and nucleoplasm. At leading order, these sources are dipoles of equal and opposite forces acting either both on the solvent, both on the polymer, or one on each fluid. We find that source of the third type produce larger flows than the other two, along with significant density fluctuations of the chromatin polymer.We then show that this type of active source, upon coarse-graining and considering long-range interactions mediated by hydrodynamics, develops spontaneous polar alignment, driving coherent motion of the chromatin when the force density injected by the active dipoles is taken above a critical value. We find that the resulting instabilities support both steady transverse flows as well as longitudinal traveling waves. Afterwards we take this further, and investigate the effect of confinement on the model dynamics. We successfully solve the system in a spherical confining geometry, and find that the resulting coherent flows of chromatin, as observed in experiments, scale with system size. We thus provide a simple physical model which reproduces the phenomenology of collective motion as had been observed in experiments.Finally, we use this newfound understanding of the active chromatin system to investigate interactions between chromatin and nucleoli. It has been previously shown that nucleoli, which are liquid droplets immersed in the nucleus, exhibit an anomalous distribution of volumes. Using a combination of microscopy data and simulations, we show that an effective attraction generated by the active dynamics of chromatin can account for this anomalous volume distribution.
Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023
Mode of access: World Wide Web
ISBN: 9798379775452Subjects--Topical Terms:
516296
Physics.
Subjects--Index Terms:
ChromatinIndex Terms--Genre/Form:
542853
Electronic books.
Universal Properties and Phase Transitions in Chromatin Dynamics.
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In the nucleus of each living cell resides its genome, which contains the information necessary for the cell to function and reproduce. This takes a polymeric form known as chromatin, organized in a complex hierarchical structure compacted within the cell nucleus. Chromatin is organized and behaves differently depending on the cell type in question, while maintaining certain fundamental structural properties. This polymer is subject to a variety of active processes such as DNA repair, transcription, and replication, driving both its organization and dynamics far from thermodynamic equilibrium. Therefore beyond its biological significance, chromatin is interesting from a physical perspective as it is an example of an active polymer system sustained in an out-of-equilibrium state. Therefore, the study of chromatin dynamics can be enlightening both for the study of active materials as well as basic biological science.In this thesis, we investigate which dynamical properties of chromatin are universal among different types of cells. Furthermore, we seek to identify the physical nature of the transitions between the different dynamical states of chromatin. Once these have been identified, we seek to develop a physical model which can capture these universal properties. In Chapter 4, we study the changes in chromatin material properties upon cell differentiation. We show that chromatin undergoes a local sol-gel transition when the cell differentiates from a stem cell to a neuron. This transition is characterized by a significant changes in the chromatin compaction profile, along with corresponding changes in both local and global dynamics.We begin by studying the dynamics of chromatin in five different cell lines, and seek to identify which dynamical and material properties are shared among them. We find that the chromatin in all five cell lines forms coherent regions at long times, the size of which is set by the size of the cell nuclei. The viscoelastic moduli of the chromatin in the differentiated cell lines are the same up to rescaling time by their relaxation time, and rescaling viscosity by heterochromatin fraction.We then develop a theoretical framework to underpin this observation of universality. We begin by considering the possible types of activity that could act on a two-fluid system such as chromatin and nucleoplasm. At leading order, these sources are dipoles of equal and opposite forces acting either both on the solvent, both on the polymer, or one on each fluid. We find that source of the third type produce larger flows than the other two, along with significant density fluctuations of the chromatin polymer.We then show that this type of active source, upon coarse-graining and considering long-range interactions mediated by hydrodynamics, develops spontaneous polar alignment, driving coherent motion of the chromatin when the force density injected by the active dipoles is taken above a critical value. We find that the resulting instabilities support both steady transverse flows as well as longitudinal traveling waves. Afterwards we take this further, and investigate the effect of confinement on the model dynamics. We successfully solve the system in a spherical confining geometry, and find that the resulting coherent flows of chromatin, as observed in experiments, scale with system size. We thus provide a simple physical model which reproduces the phenomenology of collective motion as had been observed in experiments.Finally, we use this newfound understanding of the active chromatin system to investigate interactions between chromatin and nucleoli. It has been previously shown that nucleoli, which are liquid droplets immersed in the nucleus, exhibit an anomalous distribution of volumes. Using a combination of microscopy data and simulations, we show that an effective attraction generated by the active dynamics of chromatin can account for this anomalous volume distribution.
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