Date of Award

12-31-2014

Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)

Department

Physics, Applied

First Advisor

Jonathan Celli

Second Advisor

Stephen Arnason

Third Advisor

Chandra Yelleswarapu

Abstract

Cancer is a complex disease in which growth and progression is governed by biological as well as physical cues from surrounding cells and tissues. In this thesis three dimensional cell culture models of pancreatic cancer are used in an effort to decipher the intertwined roles of physical properties (rigidity and adhesion) and biological functions of the extracellular matrix (ECM) in regulating growth and treatment response. We have used mixtures of commercial basement membrane and collagen matrices to study the effect of ECM rigidity on tumor growth and morphology. Plating PANC-1 cells on theses matrices revealed a strong correlation between stiffness (increased collagen content) and tumor growth behavior. However, since matrix adhesion may also change as a result of varying concentration, we also studied the extreme case where there is no adhesion by growing non-adherent spheroids on agar beds with and without ECM proteins diluted in media. The latter component restores the presence of the same ECM proteins as biological signaling partners, but with insufficient concentration to form a hydrogel with solid-like mechanical response. The introduction of ECM proteins diluted in the media resulted in robust, spherical and chemo-resistant PANC-1 spheroids with multiple practical applications discussed further herein.

Comments

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