Experimental and computational investigations into the mechanics and patterning of adhesive multicellular systems
Abstract/Contents
- Abstract
- Cell adhesion is one of the fundamental building blocks of multicellular organisms, and is crucial to their functioning. Creating and harnessing cell adhesion for engineering purposes is the complex challenge that animates my work in this thesis. In the first part of my work, I will describe my study of a complex multicellular organism, the zebrafish embryo, in which I took advantage of the organism's cell adhesion system to attempt to measure forces between adhering cells. For this work, I used a molecular tension sensor created by fusing the epithelial cell adhesion molecule (EpCAM) with a quantitative fluorescence resonance energy transfer (FRET) Tension Sensor Module (TSMod). Using fluorescence lifetime imaging (FLIM) in combination with FRET, I validated the in vivo expression of the sensor and its localization to the membranes of epithelial cells in the embryo, showed using fixed-length controls that the TSMod construct is appropriate for use in the zebrafish embryo, and quantified various sources of error. Overall, we achieved a FLIM resolution of 50ps, which translates to a resolution of 1pN of force. We determined that the EpCAM-TSMod was not holding any statistically significant amount of force, which is consistent with more recent findings that EpCAM may not actually be a cell adhesion molecule at all and therefore would not hold force. However, our imaging methods and analysis should prove useful for future work in the field. In the second part of my work, I built a computational simulation of a synthetic bacterial cell-cell adhesion system that was experimentally created by my colleague David Glass. After evaluating many existing modeling tools, I chose to build my simulation using the Chipmunk/Pymunk physics library. My simulation combines cell adhesion with bacterial run-and-tumble motion as well as cell growth and division, a combination which to our knowledge has not yet been achieved. I was able to reproduce Glass's experimentally-observed patterns of differential adhesion, phase separation, and coaggregation bridging. In sum, my work demonstrates that cell adhesion is a tool we can use, whether it is to build multicellular organisms or to study other scientific phenomena.
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 | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Malinas, Melanie Rose |
|---|---|
| Degree supervisor | Riedel-Kruse, Hans |
| Thesis advisor | Riedel-Kruse, Hans |
| Thesis advisor | Huang, Kerwyn Casey, 1979- |
| Thesis advisor | Huang, Possu |
| Degree committee member | Huang, Kerwyn Casey, 1979- |
| Degree committee member | Huang, Possu |
| Associated with | Stanford University, Biophysics Program. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Melanie Malinas. |
|---|---|
| Note | Submitted to the Biophysics Program. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Melanie Rose Malinas
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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