Graduation Year

2006

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Physics

Major Professor

Garrett Matthews, Ph.D.

Committee Member

William S. Dalton, Ph.D.

Committee Member

Sarath Witanachchi, Ph.D.

Committee Member

Myung K. Kim, Ph.D.

Committee Member

Chun-Min Lo, Ph.D.

Keywords

Biopolymer, Bioengineering, Proteoglycans, Heparanase, Biophysics

Abstract

The study of the processes relating glycobiology and cancer will have increased interest in coming years. To contribute to this trend the outcome of this work will be useful for investigations in glycobiology, using experimental methods exhibiting controlled carbohydrate composition, organization, and orientation, drawn from materials science and physics and that can be used in bioengineering and other technical areas in biology.

In this work, the focus has been on physical studies of some members of the family of glycosaminoglycans and their role in cancer metastasis. The project studies the static adhesion of cancer cells to substrates functionalized with cell surface glycocalyx molecules and, in particular, in the interaction of heparan sulfate, keratan sulfate and chondroitin sulfates with the cells. Surface characterization techniques are used to analyze the structure of the polymeric brushes deposited on the substrates.

The hypothesis that the adhesion of whole cancer cells to glysocaminoglycan substrates is a function of polysaccharide charge per dimer and chain length was proposed and tested.Part of the work has been dedicated to study the changes in the adhesion of tumor cells inthe presence of heparanase, an enzyme expressed in the tumor cell surface.The essential achievements of the project have been:

a) Design of a new a method for the deposition and patterning of glycans to glass or silicon surfaces functionalized with a silane agent, exposing an amino terminated monolayer as functional substrate.

b) Development of a new method for the calculation of the density of the deposited molecules.

c) Physical characterization of the surfaces using a combination of surface science techniques, including ellipsometry and atomic force microscopy. These surfaces should be useful for developing additional experiments that may be helpful in understanding the adhesive properties of the cells.

d) Comparative analysis of the behavior of cancer cells to the functionalized surfaces, specifically the study of the static adhesion of the cells, in the presence or absence of the surface protein heparanase or its inhibitors.

e) Confirmation of the hypothesis that attachment of whole cancer cells, in vitro, depends linearly on the charge per dimer of polysaccharide.

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