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In vitro and in silico findings on cell-cell and cell-ECM interactions during cellular aggregation and rearrangement
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Title
In vitro and in silico findings on cell-cell and cell-ECM interactions during cellular aggregation and rearrangement
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ETD_2033
Identifier
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000051787
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eng
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theses
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Topic
Biomedical Engineering
Subject
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Topic
Cell aggregation
Subject
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(authority = ETD-LCSH)
Topic
Cell interaction
Abstract
In this dissertation, we present in silico and in vitro work on the dynamics of cellular aggregation and rearrangement as cell-cell and cell-ECM interactions are systematically varied. Computationally, we explore the contributions of homotypic and heterotypic forces between cells and the ECM affect cellular self-assembly. We find that variation of homotypic and heterotypic forces generates both expected morphologies and previously unreported patterns. Among the newly discovered patterns are segmented states of alternating cell types, and an “onion” state, in which cells form multilayer-aggregates of two cell types. Experimentally we varied cell-ECM adhesive strength through selection of α5β1-integrin receptor expression in Chinese Hamster Ovary (CHO) Cells at two soluble fibronectin (sFn) concentrations. Second, to describe dual adhesive relations, we used a CHO cell line variants coexpressing integrin and N-cadherin surface receptors. We found previously unreported complex behaviors of aggregates in these experiments. For example, we found that at constant sFn concentration, aggregate cohesion grows linearly as α5β1 receptor density is increased from low to moderate levels. However, further increase in receptor expression causes an abrupt drop in tissue cohesion. We propose that the observed biphasic property of these aggregates may be due to depletion of sFn below a critical value in the aggregate microenvironment at high α5β1 expression level. We also found that a complicated interplay emerges when cell-ECM and cell-cell interactions mediate cellular aggregation and rearrangement. Thus, we describe two nodes of cellular interaction, cell-ECM and cell-cell/cell-ECM. For weak cell-ECM interactions, cells can still rearrange, and new cellular patterns (e.g. inverted structures) emerge. For high cell-ECM strengths, cells are bound to the matrix and cannot rearrange. For weak and high cell-ECM interactions, cell-cell governs final equilibrium configurations. We propose that these results have potential implications for embryonic development, for wound healing, and for cancer therapeutic applications.
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electronic resource
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xii, 159 p. : ill.
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Ph.D.
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Includes bibliographical references
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by Carlos Eduardo Caicedo-Carvajal
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Caicedo-Carvajal
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Carlos Eduardo
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1976
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author
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Carlos Eduardo Caicedo-Carvajal
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Shinbrot
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Troy
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chair
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Advisory Committee
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Troy Shinbrot
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Foty
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Ramsey
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co-chair
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Advisory Committee
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Ramsey A Foty
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Roth
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Charlie
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internal member
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Charlie Roth
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Corbett
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Siobhan
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Advisory Committee
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Siobhan Corbett
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Rutgers University
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degree grantor
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Graduate School - New Brunswick
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school
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2009
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2009-10
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xx
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Rutgers University Electronic Theses and Dissertations
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ETD
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Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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Identifier
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doi:10.7282/T35Q4W8R
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ETD doctoral
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Rights
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The author owns the copyright to this work
Copyright
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Copyright protected
Notice
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Open
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Permission or license
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Caicedo-Carvajal
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Carlos
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Carlos Caicedo-Carvajal
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Rutgers University. Graduate School - New Brunswick
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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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