(137d) Regulation of Focal Adhesion Maturation and Cell Edge Dynamics by Epidermal Growth Factor

Cell migration plays an essential role in many processes such wound healing, immune response and cancer metastasis. During cancer metastasis, cells are directed to migrate out of the tumor through the integration of both contact guiding cues (collagen) and chemotactic cues (EGF). This integration occurs through the regulation of focal adhesion (FA) maturation and protrusion dynamics, which are connected through intracellular signal transduction feedback loops. FAs exist in different maturation states which are defined by their size and protein density. It is thought that these characteristics determine the magnitude of the signal for protrusion. Conversely, protrusion enhances FA assembly and the initial stages of FA maturation. Both collagen and EGF regulate adhesion and protrusion globally; however it is not known how these inputs locally control the feedback loop between FA maturation and protrusion. We are using fluorescence microscopy and image analysis techniques to examine the correlation between FA dynamics and cell edge dynamics in a rat mammary adenocarcinoma cell line under different doses of EGF. Cell speed, edge dynamics and focal adhesion number linearly increase with EGF concentration, whereas FA intensity is inversely related to EGF concentration. Interestingly, local fluctuations in these parameters over time can be analyzed in order to understand how FA maturation and protrusion regulate each other. Our goal is to use this analysis in instances where cells integrate both contact guidance and chemotaxis cues.