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The overexpression of Mucin-1 (Muc1), a member of the mucin transmembrane family of biopolymers, is among the most common genetic manifestations of cancer. Owing to its ubiquity amongst cancer subpopulations, the role of Muc1 has been extensively studied at a cellular level. However, much of this characterization has focused on Muc1's role in signaling cascades, ignoring the potential physical ramifications that the overexpression of this large biopolymer may have on its molecular environment. This work aims to discern some of the means through which Muc1 acts as a physical actuator. We first looked towards Muc1’s role at the cancer cell surface, where its overexpression leads to an accumulation of negative charges at the plasma membrane. We aimed to create a tool to characterize whether these negative charges lead to excess proton accumulation and subsequently acidification of the mucin environment. To this end, we designed a recombinant protein-based pH sensor and found that we could accurately measure pH on a mucin-rich cell surface environment by applying our sensor. Subsequently, we explored the intracellular biophysical consequences of Muc1 overexpression. We showed that during its synthesis, Muc1 is preferentially accumulated within the endoplasmic reticulum and regulated its morphology through negative curvature generation. Finally, we showed that the polymeric domain of Muc1, when expressed in the lumen of the endoplasmic reticulum, is capable of generating a vesiculated endoplasmic reticulum structure, facilitating the analysis of diseases with similar morphologies. Taken together, this work highlights the capacity of Muc1 to regulate its cellular environments throughout the entirety of the cell through biophysical forces, in the hopes of informing future inquiry into the roles of Muc1 in cancer.

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150 pages


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Union Local


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Paszek, Matthew

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DeLisa, Matthew
Alabi, Christopher
Lammerding, Jan

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Biomedical Engineering

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Ph. D., Biomedical Engineering

Degree Level

Doctor of Philosophy

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Government Document




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dissertation or thesis

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