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Dynamics and Structure of Cellular Aggregation
This work provides new insights into the dynamics and structure of cellular aggregation. Starting from cell motility which is necessary to get the cells into close proximity it presents new tools for visualization, analysis and modeling of aggregation processes. While a lot of work has been done...
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| Format: | Doctoral Thesis |
| Language: | English |
| Published: |
Philipps-Universität Marburg
2015
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| Subjects: | |
| Online Access: | PDF Full Text |
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| Summary: | This work provides new insights into the dynamics and structure of cellular aggregation. Starting
from cell motility which is necessary to get the cells into close proximity it presents new
tools for visualization, analysis and modeling of aggregation processes.
While a lot of work has been done in the field of microbial and amoeboid motility, there is
a lack in theoretical understanding of mammalian cell motion, especially concerning directed
migration stirred by external cues. To close this gap I developed a two-dimensional generic
model based on mechanical cell-substrate interactions. This model facilitates the discrete nature
of the motion cycle of mammalian cells by a randomized growth of protrusions and their
retraction depending on the strength of an external cue. This model is capable of reproducing
most experimental observations, especially the behavior at sharp changes in strength of the
external cues, and provides an explanation for the attachment of the lagging cell pole as it
increases the efficiency of gradient sensing.
Furthermore, I introduce new experimental methods to visualize and analytical toolkits to
analyze the structure of the highly irregular cell aggregates. These approaches were tested in
two example cases: the two dimensional aggregation of mouse embryonic fibroblast (MEF)cells and the flocculation of S. cerevisiae mediated by the sugar-dependent adhesion protein
Flo5.
While it was possible to achieve temporal information of the MEF cell aggregation, the
flocculation of S. cerevisiae is not accessible in this way.
The time-lapse microscopy series indicate a subdivision of MEF cell aggregation into a
spreading and a contraction phase. In addition, the data shows that there is a dependency of
the aggregate’s structure on its size with a sharp transition from a linear dependency to a
constant structure.
The three-dimensional imaging of immobilized flocs using a confocal laser scanning microscope
provided information about the structural properties of yeast flocs. The most important
findings are that the flocs are self similar fractal structures and that cheater cells, i.e. cells that
do not produce the necessary binding proteins but benefit from the altruistic behavior of producing
cells, are largely underprivileged in the process. This indicates that, even though flo5
does not qualify as a “green beard gene” by definition, the benefits of the resulting altruistic
behavior are strongly shifted in favor of the producing cells by the aggregation mechanism. |
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| DOI: | 10.17192/z2015.0211 |