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3D-stiffness microenvironment leads to nuclear envelope rupture, DNA damage, and genome variation / Kuangzheng Zhu.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Zhu, Kuangzheng, author.
- Language:
- English
- Subjects (All):
- Biophysics.
- Biomedical engineering.
- Bioengineering.
- Chemical engineering.
- Chemical and biomolecular engineering--Penn dissertations.
- Penn dissertations--Chemical and biomolecular engineering.
- Local Subjects:
- Biophysics.
- Biomedical engineering.
- Bioengineering.
- Chemical engineering.
- Chemical and biomolecular engineering--Penn dissertations.
- Penn dissertations--Chemical and biomolecular engineering.
- Physical Description:
- 1 online resource (205 pages)
- Contained In:
- Dissertations Abstracts International 83-08B.
- Other Title:
- Three-dimensional stiffness microenvironmentlLeads to nuclear envelope rupture, DNA damage, and genome variation
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2021.
- Language Note:
- English
- System Details:
- Mode of access: World Wide Web.
- Summary:
- Solid tumor cells grow in a stiff microenvironment with dense extracellular matrix (ECM) and condensed packing of adjacent cells. Tumor cells are capable of migrating through constricted pores formed by ECM or surrounded by other cells, and the nuclear envelope can break with repair factor mislocalization, further leading to DNA damage and genetic changes, or even accumulated to be genomic variations. Cell division, likewise, is confined by a stiff niche of adjacent cells and extracellular matrix, and such confinement has been reported to cause chromosome missegregation. The chromosome-loss live cell reporter system was developed to prove that cells undergoing specific types of chromosome missegregation can survive and maintain heritability, resulting in permanent genomic variations. Mitotic cells under in vitro confinement and in vivo conditions exhibit more abnormal division and more fluorescence-null reporter-negative cells, for both cancer and normal types. Confinement and SAC inhibition both lead to chromosome missegregation but do not superimpose, and Topoisomerase IIa plays an essential role in cells to survive after confined mitosis. Myosin II was found to lead to increased nuclear envelope rupture and, therefore, more DNA damage, while it protects mitotic cell rounding within 3D confined environments, since the increase of reporter-negative cells was observed after Myosin II knockdown.
- Notes:
- Source: Dissertations Abstracts International, Volume: 83-08, Section: B.
- Advisors: Discher, Dennis; Committee members: Radharishnan, Ravi; Crocker, John C.; Janmey, Paul.
- Department: Chemical and Biomolecular Engineering.
- Ph.D. University of Pennsylvania 2021.
- Local Notes:
- School code: 0175
- ISBN:
- 9798780646396
- Access Restriction:
- Restricted for use by site license.
- This item must not be sold to any third party vendors.
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