Graduation Year

2010

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Electrical Engineering

Major Professor

Ryan Toomey, Ph.D.

Co-Major Professor

Jing Wang, Ph.D.

Committee Member

Ashok Kumar, Ph.D.

Committee Member

Mark Jaroszeski, Ph.D.

Committee Member

Garrett Matthews, Ph.D.

Keywords

biomaterials, cells, bioadhesion, thermoresponsive, polymers

Abstract

Lung cancer has the highest mortality rate relative to all types of cancers, and unfortunately there still exist numerous challenges towards decreasing this rate. One of these challenges is gaining a clear understanding of why metastatic lung cancer cells attach and detach to colonize other areas of the body. Reports suggest that the attachment of cells to secondary tumor sites does not occur randomly. It is theorized that both the physical and chemical properties of the tissue are able to create a suitable environment for their adhesion. Therefore, the motivation for the work presented herein is to use dynamic thermoresponsive polymer surfaces as a tool towards unraveling this seemingly mysterious behavior of metastatic cancer cells. This type of polymer is able to swell and deswell as a function of temperature. As such, spin-cast thin films of this polymer provide for topographies that have been used to investigate how highly metastatic lung cancer cells are able to rearrange their structure, specifically the cytoskeleton. Changes in cell to surface anchorage as a function of thin film structure can also monitored.

One of the most studied reversibly binding surfaces is poly(Nisopropylacrylamide) (PNIPAAm), which has been considered for the past two decades as a non-destructive method for the harvest of confluent cell sheets. As a result of this property, a series of photocrosslinkable copolymers based on PNIPAAm and methacroyloxybenzophenone (MaBP) have been developed. Coatings are created by spin-casting the polymer followed by ultraviolet (UV) radiation, which triggers the transition in the benzophenone groups. This leads to the formation of a biradicaloid triplet that abstracts a hydrogen from a neighboring aliphatic C-H group, leading to a stable C-C bond. The characteristics of the polymer film, i.e. thickness, pattern, and topography, can be tuned during the spin casting and subsequent exposure/ developing process.The ease of tunability of this polymer allows for the investigation of the aforementioned parameters and their possible effects on bioadhesion.

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