(489h) Timing and Spatial Control of Epidermal Growth Factor-Mediated Focal Adhesion Maturation and Cell Edge Dynamics

Migration is an important cellular response that has varied effects in vivo. It mediates physiological processes such as wound healing as well as pathological processes such as cancer metastasis. Cells migrate by cycling between protrusion, adhesion, contraction and retraction. While the cycling time appears to vary in different cell lines and under different environmental conditions, the cycling time in a particular context is surprisingly regular, suggesting a high degree of temporal control. Additionally, these cycles occur on length scales smaller than the cell, indicating a high degree of spatial control. Focal adhesions are thought to contribute to the organization of these cycles by inducing signals for either protrusion or retraction based on their maturation state. Focal adhesions are formed though interactions between the cell and the extracellular matrix, but the maturation state can be regulated by soluble promigratory proteins such as epidermal growth factor (EGF). While the effects of EGF on cell migration have been well-studied, how EGF cooperates with or controls focal adhesion-mediated signals for protrusion and retraction is unknown. We are using high-resolution fluorescent light microscopy techniques to examine the spatial and temporal correlation between protrusion and retraction rates and focal adhesion maturation states under different doses of EGF. The temporal and spatial control by EGF over cycles of protrusion, adhesion, contraction and retraction may have important consequences for in vivo migration, particularly in the context of chemotaxis, where gradients of EGF are known to spatially bias cell migration.