Mechanical regulation of E-cadherin adhesion and signaling in epithelia

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Abstract/Contents

Abstract
Mechanical force has been shown to regulate the shape and size of tissues in multicellular organisms. Cells within the tissue can respond to mechanical stimuli and elicit a downstream signaling response called mechanotransduction. One of the many protein complexes that sense and respond to mechanical force in epithelial cells are E-cadherin cell-cell junctions. E-cadherin links neighboring cells, and through its interaction with catenin proteins, is a signaling hub for many pathways involved in cell proliferation, differentiation, and migration, and tissue morphogenesis. The focus of my thesis was to study how E-cadherin responds to changes in mechanical force and the role of tension in regulating downstream cellular processes. We showed that changes in mechanical force is balanced between both cell-cell junctions and cell-extracellular matrix (ECM) junctions in cell pairs. We also developed a cell stretching system as a technology for studying the role of mechanical force in epithelial tissue biology. We observed that mechanical stretch can regulate cell cycle progression through the phosphorylation and nuclear localization of β-catenin. Also uniaxial mechanical stretch can orient the mitotic spindle in the direction of stretch through the mechanosensitive E-cadherin/LGN complex. Altogether, my thesis provides more understanding of how cell-cell junctions respond to mechanical force and the role of mechanical force in E-cadherin-regulated cell cycle and cell division.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2018; ©2018
Publication date 2018; 2018
Issuance monographic
Language English

Creators/Contributors

Author Hart, Kevin
Degree supervisor Nelson, W. J. (W. James)
Thesis advisor Nelson, W. J. (W. James)
Thesis advisor Feldman, Jessica L
Thesis advisor O'Brien, Lucy
Thesis advisor Weis, William I
Degree committee member Feldman, Jessica L
Degree committee member O'Brien, Lucy
Degree committee member Weis, William I
Associated with Stanford University, Department of Biology.

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Kevin Hart.
Note Submitted to the Department of Biology.
Thesis Thesis Ph.D. Stanford University 2018.
Location electronic resource

Access conditions

Copyright
© 2018 by Kevin Charles Hart
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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