Cordintion of Spatial an Temporal Regulation of Integrin and EGFR Signaling

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Cells respond to their environment by transmitting extracellular signals to the inside of the cell via different classes of transmembrane receptors. While integrin receptors are engaged by extracellular matrix (ECM) components to mediate cell adhesion, receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR) are activated by specific peptide ligands. The integration of these different signals determines the cellular response, whether it be survival, proliferation, differentiation, or migration. Rather than studying these signals in isolation, we will employ a systematic approach to determine how the spatial and temporal presentation of ECM and growth factor ligands cooperate to activate their receptors and trigger downstream signaling pathways. Using a novel nanolithographic technique we are able to position anchor points for adhesion relevant ligands with nanometer precision, allowing the spatial control of integrin engagement along the cell membrane. These ligand patterns can also be transferred onto mechanical expandable elastomer substrates, which allow the dynamic variation of the ligand distance. Using this experimental system, we will study how the chemical structure of the ECM impacts on growth factor signaling and, vice versa, how immobilized growth factors like EGF modulate integrin clustering and focal adhesion assembly, ultimately regulating cellular responses in a coordinated fashion.