Substrates for Mechanistic Studies of Cell Adhesion

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DESCRIPTION: (Applicant's Description) This research program will investigate the molecular interactions underlying the adhesion and migration of mammalian cells on the protein extracellular matrix. Proper ligand-receptor interactions are required for guiding the formation of tissue structure in development and also for maintaining the integrity of tissue. The loss of proper interactions between cells and the protein matrix plays a role in cancer and in many other diseases. This research will develop a class of model substrates based on self-assembled monolayers of alkanethiolates on gold that can control entirely the immobilized ligands with which cell surface receptors interact. These substrates will be used to characterize ligands of the extracellular matrix that are important in adhesion and will investigate the mechanisms by which cells respond to these ligands. The research will be directed towards three goals. Substrates presenting Arg-Gly-Asp peptides and related analogs will be used to investigate the importance of dynamic processes of integrin-receptor interactions in cell adhesion and migration. A second theme will use monolayers to investigate the mechanisms by which orphan ligands direct cell attachment. A third effort will use substrates presenting an array of hundreds of peptides to identify new ligands that are important in adhesion and migration.