Peptide microarrays for the discovery of cell-ligand interactions that direct cell state

Biomaterials;Peptide;Microarray;Cancer;Differentiation;De-differentiation;Materials

Zhang, Douglas

关键词: Biomaterials;    Peptide;    Microarray;    Cancer;    Differentiation;    De-differentiation;    Materials;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/95253/ZHANG-DISSERTATION-2016.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

During development, cells receive many cues from their environment. These cues, whether physical or chemical in nature, are able to regulate the behavior of cells from macroscale levels such as tissue organization, to microscale levels such as gene modifications. Synthetic materials are able to similarly affect cell phenotype, and recent advances in microarray technology has allowed the systematic investigation of a large combinatorial space of material properties. As we gain new insights on the effects of chemical structures and physical properties, controlling the interaction between these various components at the cell-material interface will be invaluable in developing new materials for biomedical devices and tissue engineering applications. The aim of this project is to develop a peptide array to screen for specific cell-ligand interactions. We synthesize a library of peptides that are derived from extracellular matrix proteins and serve as a highly scalable synthetic microenvironment. We demonstrate that by displaying combinations of peptides on the surface of self-assembled monolayers, we can affect stem and cancer stem cell fate. In chapter 2 we demonstrate that self-assembled monolayers provide a facile method for modulating cell phenotype. In chapter 3 we incorporate peptide ligands at the cell-monolayer interface and show that ligand affinity can regulate differentiation. In chapters 4 and 5 we present a high-throughput array platform that allows combinatorial investigation of a library of biomimetic peptides. We report that the array platform is capable of screening for cancer stem cell phenotypic changes in response to the underlying substrate. We are able to identify a specific combination of peptides that selectively enhance the expression of several putative melanoma cancer stem cell markers and enhance invasiveness and tumorigenicty. Such a platform will be useful as in vitro drug screening models to identify therapeutic targets.