Using well-defined model surfaces to study cell adhesion

The work presented in this dissertation uses self-assembled monolayers as the platform for creating model substrates of the extracellular matrix in order to gain a clear picture of how cells attach and respond to their microenvironment. Two studies that took advantage of the control monolayer substrates have over ligand presentation are described, revealing important details about cell adhesion that more traditional substrates have been unable to provide. The first study addressed the synergistic versus competitive mechanisms of cell adhesion to monolayers presenting specific type III domains of the extracellular matrix protein fibronectin. This study confirmed that the RGD and PHSRN peptide ligands within fibronectin can independently and competitively mediate cell adhesion, although the PHSRN ligand is unable to sustain adequate cell spreading and signaling on its own. The second study focused on the integrin family of cell receptors and how the process of outside-in integrin activation can be influenced. This study utilized monolayer substrates presenting two different RGD ligands and revealed that increasing the binding affinity of the ligand alters the integrin equilibrium to favor more activated integrins. Overall, using self-assembled monolayers as model substrates in cell adhesion studies removes the ambiguities from which most other methods suffer due to their inability to present the extracellular matrix ligands in a well-controlled manner.