Date of Award

1-1-2010

Document Type

Campus Access Dissertation

Department

Chemistry and Biochemistry

Sub-Department

Chemistry

First Advisor

Caryn E. Outten

Abstract

Increasing number of researchers are introducing viruses as primary building blocks to generate ornate nanomaterials for a wide-range of applications. The viruses possess highly ordered structures with well-characterized three-dimensional structures at near-atomic resolutions, batch to batch consistency, simple purification processes, and genetic and chemical modalities that confer numerous advantages for the viruses that are not often available other materials in this size range. For example, the modification of a spherical or rod-shaped virus with small molecules would present the ligands (i.e. a tripeptide motif, Arg-Gly-Asp, for cell adhesion) with different spatial densities with nanometer precision. Furthermore, given the immense diversity of viruses and virus-like particles, one could find an ideal model that is well-suited to generate a variety of spatial arrangements of ligands. Herein we present an novel platform with viruses containing integrin-binding peptides (GRGDSPG), to study how these ligands with nanoscale ordering can affect cell adhesion, spreading and mesenchymal stem cell differentiation. Previous studies have largely relied on polymeric display systems with clusters of ligands to probe cellular response, but the spatial resolution of polymeric display is limited due to its heterogeneity. The virus display system, being a monodispersed particle, is an ideal tool that allows for superior nanometer scale control. Our findings with the virus-display system reveal that ligand clusters spaced with 2-3 nanometers result in cellular morphological changes, starting from adhesion to spreading, as well as cell differentiation. These results suggest that clusters of ligands on the viruses induce different cellular activities by activating a cluster of the receptors versus a single ligand/receptor event. These cellular events could lead to new insights in some of the fundamental questions in cell differentiation, tumorigenesis and tissue/organ development.

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