Publisher: The Ohio State University



Series/Report no.: The Ohio State University. Department of Mechanical and Aerospace Engineering Undergraduate Research Theses; 2014



Abstract:

The human body is composed of trillions of cells, which are the fundamental units of life. Understanding cell-cell communication is essential in developing effective therapies for a variety of diseases, including cancer. Current experimental approaches, such as ligands presented in solution, lack the ability to describe cell-cell communication because they do not accurately mimic ligand immobilization nor do they make it possible to examine the effects of ligand biophysical properties such as quantity or spatial arrangement. In order to better mimic ligand-receptor interactions during cell-cell communication, a novel nanotechnological device recently developed in the Nanoengineering Biodesign Laboratory. This device, called a Ligand Presentation Platform, is a DNA origami engineered structure that enables precise control over quantity and spatial arrangement of ligands presented to a cell surface. Precise structure folding and ligand attachment was confirmed using gel electrophoresis and transmission electron microscopy. Functional response was examined by adding nanostructures loaded with anti-CD40 antibody to B cells transfected with Cignal GFP-NF-κB reporter construct. A significant functional response up to 4-fold higher than relevant controls was observed via single cell epifluorescence. These results demonstrate that the Ligand Presentation Platform can induce a cellular functional response, making it possible to use the nanostructure to examine the influence of spatial arrangement and quantity to provide detailed mechanistic insight that can ultimately be utilized to design molecular therapeutics that target growth and survival signaling networks in cancer cells.