SPATIOTEMPORAL PATTERNS IN POPULATIONS OF DICTYOSTELIUM DISCOIDEUM
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Pattern formation is widely observed in nature. One organism that shows spectacular
patterns is Dictyostelium discoideum (D.d.). When nutrients are available
in plenty, D.d. lead solitary lives - they feed and divide. However, when a population
of D.d. begins to starve, the cells become social. Each cell emits a chemical
called cyclic adenosine monophosphate (cAMP), which diffuses in the medium.
When neighboring cells detect cAMP, they also secrete cAMP. An enzyme phosphodiesterase,
secreted by the cells, degrades cAMP. The system is therefore a
reaction-diffusion system. After a few hours of signaling, the response of the
cells to cAMP is seen either as large scale spiral waves or target patterns. The
waves persist for about 2h. Towards the end, the cells aggregate towards the
centers of the spirals and targets through chemotaxis and form mounds. These
mounds can form multi-cellular slugs which move around looking for food.
Failing to find food, the slug transforms into a fruiting body with spores on the
top. D.d. is thus a unique organism that exhibits unicellular and multicellular
behavior.
In this thesis, I analyze the effect of various parameters on the patterns
formed by D.d.. As D.d. starves, its internal biochemistry changes. This developmental
changes drastically affect the patterns. I will present results of a
systematic analysis of the effects of the developmental path on pattern formation.
Next, I considered the effects of variability in parameters in a population
on the patterns. By mixing two populations at different developmental stages, I
introduced developmental variability in the population and found that the patterns
depend on the heterogeneity in the biochemical parameters and in spatial
distribution of cells. By modifying an existing model, by introducing temporal
variations of certain biochemical parameters, I was able to simulate the experimental
results. Further, using the simulations I was able to determine that the
dynamics of the starving populations changes from being excitable to oscillatory.
This work proved that a systematic analysis of patterns can provide information
about the developmental pathways in a system. Using the idea that populations
at different developmental stages form different patterns, I performed
experiments to check for the existence of “memory.” Indeed, I found that populations
have a memory of starvation for about 1 h. These results indicate that
the biochemical parameters do not deregulate at the same time. Simulations of
the model that I modified confirmed this analysis.
In a population, the amount of cAMP produced by cells varies. Despite this
variation, the signaling mechanism is robust. Experiments to understand this
robustness revealed that signaling can occur at very low amounts of cAMP. In
fact, when a low density population of wild type cells that could not aggregate
on its own was mixed with a high density population of mutants that could
not produce cAMP, the resulting mixture aggregates. Counterintuitively, rather
than a lack of cAMP, this effect was because of insufficient amount of the enzyme,
phosphodiesterase, which degrades cAMP. Estimates of the degradation
rates confirm that phosphodiesterase is necessary for wave propagation.
In nature, the cells have to survive on various kinds of substrates. To understand
the importance of substrates for pattern formation, I performed experiments
to observe their effects. I used agar gels of various densities as the
substrate and found that as the density of the agar substrate increased the patterns
needed more time to form, and a transition from spirals to targets was
observed. However, if the cells are immersed in larger amounts of buffer, the
effect vanishes. I hypothesize that this could mean that the thin layer of buffer
over the cells is very important.
In all the simulations, I have varied the parameters by hand. To establish
a mathematically rigorous method to estimate the parameters, I have worked
with different methods of coupling data to models to optimize the parameters.
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Date Issued
2017-12-30
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Keywords
Physics; Dictyostelium discoideum; non-linear dynamics; Pattern formation
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Committee Chair
Bodenschatz, Eberhard
Committee Co-Chair
Committee Member
Sethna, James Patarasp
McEuen, Paul L.
McEuen, Paul L.
Degree Discipline
Physics
Degree Name
Ph. D., Physics
Degree Level
Doctor of Philosophy
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dissertation or thesis