The development of strategies to control the interface between biomolecules and a solid support is critical to a number of research areas, including drug discovery, tissue engineering, and gene microarray technology. In particular, tremendous effort has been extended toward interfacing material science with cell biology to conduct mechanistic cell adhesion, polarization, and migration studies. These investigations require the combined use of a model substrate that mimics the complex nature of the extracellular matrix and a synthetic chemical immobilization methodology to pattern biospecific, biomolecular cues for cellular recognition. Currently, self-assembled monolayers (SAMs) of alkanethiolates on gold represent the most well-studied and developed surface systems in biointerfacial science, enabling the design and implementation of complex, dynamic substrates for controlling biological interactions at the molecular level.
This research is focused on employing chemoselective chemistry to engineer materials and cell surfaces for the control of biological interactions. Thus, smart biosurfaces and materials were manipulated to investigate peptide-cell, protein-carbohydrate, and lipid-cell interactions. A library of biomolecules was designed and synthesized to include chemoselective and bio-orthogonal functional groups, ketone and oxyamine. With this coupling methodology, biomaterials and cell surfaces were successfully engineered to examine a variety of cell behaviors, such as cell-biospecific ligand interactions, adhesion, polarization, migration, and cellular response to other cells. Chapter 1 provides an introduction to SAMs and a general discussion regarding the design and utility of dynamic SAM surfaces and for biological analyses. The use of SAMs on gold and indium tin oxide for cell adhesion studies is presented in Chapters 2 and 3, respectively. Chapter 4 demonstrates the development and application of a renewable carbohydrate microarray based on hydroquinone-terminated SAMs on gold. Hydroquinone was then incorporated with cell adhesive peptide, RGD, to survey selected carbohydrates and peptides for their combined effect on fibroblast adhesion, morphology, and migration; this data is discussed in Chapter 5. A cell-surface engineering strategy based on liposome delivery and membrane fusion to direct cell-cell contacts and generate 3D tissue-like structures is reported in Chapters 6 and 7. Finally, Chapter 8 describes my general conclusions and future research directions.
|Advisor:||Yousaf, Muhammad N., Spremulli, Linda L.|
|Commitee:||Schoenfisch, Mark H., Weeks, Kevin M., You, Wei|
|School:||The University of North Carolina at Chapel Hill|
|School Location:||United States -- North Carolina|
|Source:||DAI-B 73/01, Dissertation Abstracts International|
|Subjects:||Cellular biology, Biochemistry|
|Keywords:||Bioactive surfaces, Cell behavior, Cell-surface engineering, Extracellular matrix, Liposome fusion, Self-assembled monolayers|
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