Exam Committee: Robert H. Austin (advisor), Kirk McDonald, and Suzanne Staggs Traditional cancer research has hunted for "the" crucial mutations alleged to unleash "rogue" cells. The Princeton Physical Sciences-Oncology Center (PS-OC) is one of twelve National Cancer Institute centers looking for new perspectives to address the imprecision of prognosis and the evolution of drug resistance that remain concerns in current research. One emerging perspective is that cancer is not merely a "disease of the genes," but also a product of cell-cell interactions and cell-microenvironment interactions. A complementary perspective is that malignant behaviors are not constructed "from scratch," but rather are throwbacks to phenotypes that bene ted early multi-cellular populations before being suppressed to allow the evolution of more recent multi-cellular organisms. Thus, simpler microorganisms might model multi-cellular behaviors relevant to cancer. One thrust distinguishing Princeton's PS-OC is the use of E. coli bacteria in microfabricated structures as a model for mammalian cell populations. In this thesis, we model cell-environment and cell-cell interactions in E. coli in microfabricated devices. In references [1] and [2], Peter Galajda observed the trapping of swimming bacteria by microfabricated funnel "fly-traps." Galajda's work raised questions about connecting the trapping of bacteria to optics. In Chapter 2, we describe bacterial trapping using a path-integral and explain how the appearance of the run-length of swimming bacteria in this classical system is related to the appearance of wavelength in quantum-mechanical path-integrals. In Chapter 3, we explain that the results of Chapter 2 depend on cellular population densities. As we reported in [3], low- and high-density inoculations can lead to trapped and traveling-band behaviors. The traveling behavior in our work is described by the same expression that produces migration in the Keller-Segel equations. However, the Keller-Segel equations describe bacterial dynamics in smooth glass capillaries, where "spreading out" and chemotactic migration, rather than trapping and migration, constitute the relevant dichotomy. We speculate that the transition between trapping and migration in Chapter 3 is more relevant to the real-life survival of bacteria because (a) natural environments contain textures and crevices and (b) many bacterial behaviors involve the This PDF is also available from the Princeton Physics department website and the ProQuest database. Posted 2010 Dec 16.
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