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Three-dimensional computational modeling of pseduopod-driven amoeboid cells through extracellular matrix geometry

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Title
Three-dimensional computational modeling of pseduopod-driven amoeboid cells through extracellular matrix geometry
Name (type = personal)
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Campbell
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Eric J.
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Eric J. Campbell
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author
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Bagchi
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Prosenjit Bagchi
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chair
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Lin
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Hao
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Hao Lin
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Advisory Committee
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internal member
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Zou
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Qingze
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Qingze Zou
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Advisory Committee
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internal member
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Parekkadan
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Biju
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Biju Parekkadan
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Advisory Committee
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outside member
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Rutgers University
Role
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degree grantor
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School of Graduate Studies
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school
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Text
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theses
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2019
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2019-05
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2019
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English
Abstract (type = abstract)
Migration of amoeboid cells is characterized by the formation of pseudopods, or extensions of the cell membrane which protrude outwards, bifurcate, and retract in a dynamic fashion. The study of the amoeboid morphology is immeasurably important, as many cells and processes within the body depend on pseudopod-based migration, such as the phagocytosing of foreign pathogens by immune cells, the extension of nerve axons during neural development, the repair of damaged connective tissue and skin by fibroblasts and epithelial cells, the migration of key progenitor cells during embryonic development, and the invasive propensity of cancer cells during metastasis. Amoeboid motility is a complex, multiscale process which involves extreme cell deformation, internalized and surface-bound biochemistry, and both cytoplasmic and extracellular fluid interactions. Additionally, cells are often immersed within a confining and complex heterogenous environment known as the Extracellular Matrix (ECM). The ECM and cell are fundamentally coupled to one another, where membrane deformability, surface protein diffusivity, fluid viscosity, matrix porosity, pore size, and alignment can alter the behavior and dynamics of a cell.
In this dissertation, a three-dimensional computational model is presented in which pseudopod-driven amoeboid migration is analyzed in various geometries, and under varying cell parameters. Models are developed for the cell membrane, pseudopod pattern generator, extracellular matrix geometry, and fluid-cell/fluid-obstacle coupling, after which a detailed analysis is performed. The approach is based on use of immersed-boundary methods, which allow for seamless integration between the highly deformable cell, fluid, and arbitrarily-shaped extracellular geometry. Amoeboid swimming is first studied through an unbounded fluid domain, revealing effects caused through the alteration of membrane deformability, surface-protein diffusivity, and fluid viscosity. A regime change in cell dynamics, allowing the cell to transition from slow, random motion, to fast, persistent motion is observed in certain parameter ranges. Cell migration through various ECM geometries is then considered, where the influence of matrix porosity and obstacle size is added to the existing analysis. In addition to drastically altered behavior, interesting cell dynamics are seen due to cell-obstacle interactions. Finally, amoeboid locomotion is studied through an expanded assortment of ECM geometries, while a weak adhesion model characteristic of an amoeboid cell is adopted. In each case, a comprehensive study of cell behavior, pseudopod dynamics, and fluid field analysis is performed. The simulated cell is shown to be qualitatively similar in form to experiments, and quantitatively similar in regard to cell speed and dynamics. Insights into cell persistence, dynamics, and migration speed are given. Overall, this model pushes the forefront of the three-dimensional computational modeling of amoeboid cells, revealing fascinating behaviors, trends, and dynamics. Its continued refinement has the potential to reveal further mechanisms of amoeboid migration and the influence of tissue geometry on its behavior.
Subject (authority = local)
Topic
Cell
Subject (authority = RUETD)
Topic
Mechanical and Aerospace Engineering
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Rutgers University Electronic Theses and Dissertations
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ETD_9722
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application/pdf
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text/xml
Extent
1 online resource (xx, 170 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = LCSH)
Topic
Amoeboid movement -- Models
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School of Graduate Studies Electronic Theses and Dissertations
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rucore10001600001
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Identifier (type = doi)
doi:10.7282/t3-mnbs-xg51
Genre (authority = ExL-Esploro)
ETD doctoral
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The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Campbell
GivenName
Eric
MiddleName
J.
Role
Copyright Holder
RightsEvent
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Permission or license
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2019-04-08 18:51:36
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Name
Eric Campbell
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Rutgers University. School of Graduate Studies
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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2019-05-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2019-11-30
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after November 30th, 2019.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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