Development of dynamic substrates for studies of cell adhesion and migration

A class of model substrates that modulate the dynamic environment for a variety of cell adhesion and migration experiments was developed. The substrate is based on an electrochemically switchable self-assembled monolayer that presents redox active hydroquinone groups. In the presence of the cells, the surface can be activated to undergo chemoselective reaction between quinone monolayers and oxyamine-tethered ligands resulting in ligand immobilization on the surface. The dynamic substrates were used to probe in real-time how the interplay between the population of cells, the initial pattern geometry, ligand density, ligand affinity and integrin composition affects cell migration and growth. The study also showed cell migration was affected by initial events which dictated subsequent motility that superseded the composition of the underlying surface chemistry. Whole genome microarray analysis indicates that several classes of genes ranging from signal transduction to cytoskeletal reorganization are differentially regulated depending on the nature of the surface conditions.;A combined photochemical and electrochemical approach generated model substrates presenting molecularly defined gradients of ligands for studying cell migration and polarization. Deprotection of a photo-labile group by ultraviolet light revealed redox active molecules in patterns and gradients; consequently so were the coupled ligand molecules. We show quantitatively the subtle interplay between ligand slope, density and affinity that causes a cell to modulate its adhesion and migration position and behavior during directed movement. The methodology for immobilizing ligand and patterning gradient was also used in producing co-culture model substrate and nanoarrays for adhesion study.