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The Contribution of Chromatin to Nuc...
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Schreiner, Sarah Marie.
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The Contribution of Chromatin to Nuclear Mechanics.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
The Contribution of Chromatin to Nuclear Mechanics./
作者:
Schreiner, Sarah Marie.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 2016,
面頁冊數:
101 p.
附註:
Source: Dissertation Abstracts International, Volume: 77-12(E), Section: B.
Contained By:
Dissertation Abstracts International77-12B(E).
標題:
Cellular biology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10158161
ISBN:
9781369131697
The Contribution of Chromatin to Nuclear Mechanics.
Schreiner, Sarah Marie.
The Contribution of Chromatin to Nuclear Mechanics.
- Ann Arbor : ProQuest Dissertations & Theses, 2016 - 101 p.
Source: Dissertation Abstracts International, Volume: 77-12(E), Section: B.
Thesis (Ph.D.)--Yale University, 2016.
The cells in our body are constantly subjected to remarkable amounts of mechanical stresses that they must accommodate and adapt to in order to maintain normal cellular functions. One of the ways in which the cells can accommodate these mechanical stresses is to distribute them into the cellular network, including their nucleus. However, the nucleus must have a means to handle and disperse forces applied to it. The nuclear lamins are considered to be the primary mechanical defense of the mammalian nucleus, however, lamins are part of an integrated network of lipids, proteins, and chromatin. Yeast, which lack a nuclear lamina, provide a model system in which to study the lamin-independent contributions of chromatin and proteins residing in the nuclear membrane to nuclear mechanics. Here, I have combined a quantitative imaging platform capable of measuring 3D nuclear contours in live cells with an in vitro optical tweezers assay to probe the mechanical properties of S. pombe nuclei. In live cells, I find that both condensed chromatin and association of chromatin with the inner nuclear membrane (INM) through integral membrane proteins is required for a normal mechanical response of the nucleus to microtubule forces. Increasing loss of integral INM proteins or loss of heterochromatin results in highly deformable nuclei specifically in response to exogenous forces from microtubules. These nuclei also show a decreased capacity to recover from mechanical stress. Using optical tweezers, I find that nuclei lacking integral INM proteins or heterochromatin are less stiff than wild type nuclei and have an increased amount of chromatin flow, particularly when force is applied at rates that recapitulate the kinetics of microtubule dynamics in vivo. Wild type mitotic nuclei, in which chromatin is globally released from the INM, are extremely soft and have increased amounts of chromatin flow. However, nuclei from cdc25-22 cells which have a decreased chromatin to nuclear volume ratio, but the same number of chromatin attachments to the nuclear periphery compared to wild type, are less stiff that wild type, but do not display increased chromatin flow. Combined with the in vivo data, this suggests that chromatin mechanically buffers cytoskeletal forces in wild type cells, but that without proper connectivity of the system in cells lacking INM proteins, chromatin can flow with the microtubule forces, causing larger, longer lasting deformations in the nuclear envelope.
ISBN: 9781369131697Subjects--Topical Terms:
3172791
Cellular biology.
The Contribution of Chromatin to Nuclear Mechanics.
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The cells in our body are constantly subjected to remarkable amounts of mechanical stresses that they must accommodate and adapt to in order to maintain normal cellular functions. One of the ways in which the cells can accommodate these mechanical stresses is to distribute them into the cellular network, including their nucleus. However, the nucleus must have a means to handle and disperse forces applied to it. The nuclear lamins are considered to be the primary mechanical defense of the mammalian nucleus, however, lamins are part of an integrated network of lipids, proteins, and chromatin. Yeast, which lack a nuclear lamina, provide a model system in which to study the lamin-independent contributions of chromatin and proteins residing in the nuclear membrane to nuclear mechanics. Here, I have combined a quantitative imaging platform capable of measuring 3D nuclear contours in live cells with an in vitro optical tweezers assay to probe the mechanical properties of S. pombe nuclei. In live cells, I find that both condensed chromatin and association of chromatin with the inner nuclear membrane (INM) through integral membrane proteins is required for a normal mechanical response of the nucleus to microtubule forces. Increasing loss of integral INM proteins or loss of heterochromatin results in highly deformable nuclei specifically in response to exogenous forces from microtubules. These nuclei also show a decreased capacity to recover from mechanical stress. Using optical tweezers, I find that nuclei lacking integral INM proteins or heterochromatin are less stiff than wild type nuclei and have an increased amount of chromatin flow, particularly when force is applied at rates that recapitulate the kinetics of microtubule dynamics in vivo. Wild type mitotic nuclei, in which chromatin is globally released from the INM, are extremely soft and have increased amounts of chromatin flow. However, nuclei from cdc25-22 cells which have a decreased chromatin to nuclear volume ratio, but the same number of chromatin attachments to the nuclear periphery compared to wild type, are less stiff that wild type, but do not display increased chromatin flow. Combined with the in vivo data, this suggests that chromatin mechanically buffers cytoskeletal forces in wild type cells, but that without proper connectivity of the system in cells lacking INM proteins, chromatin can flow with the microtubule forces, causing larger, longer lasting deformations in the nuclear envelope.
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