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Tue, 03 Apr 2012 15:13:17 -0400

Signaling Response of Neuronal Cells to 3D Tissue Scaffolds
By Dalton N. Hughes, Andreia Ribeiro, Swarnalatha Balasubramanian
Jennie B. Leach, Associate Professor, Department of Chemical Engineering

UC Ballroom | 10:00-12:30 PM

Neurons grow and develop in the three-dimensional (3D) environment of the developing embryo. Previous work from our group has demonstrated that culturing embryonic neurons in 3D matrices allows the cells to respond in a way that more closely resembles natural development than traditional two-dimensional (2D) culture. Cells interact with their extracellular matrix and sense the dimensionality of their surroundings via integrin receptors on the cell surface that bind to matrix molecules, initiate intracellular signaling cascades and affect changes in cell shape and function. Our work focuses on elucidating the signaling events that regulate these changes in cell response. We hypothesize that 3D environments impose changes in matrix-ligand organization and alter neuronal behavior by modulating β1-integrin cytoskeleton signaling. PC12 cells, a neuronal cell model, were cultured on 2D and within 3D collagen substrates and probe the signaling response by inhibiting several key signaling molecules involved in regulating neuron morphology: β1-integrin, Focal Adhesion Kinase (FAK), and an activated form of FAK that is phosphorylated at tyrosine 397. The results of this study will identify the key signaling mechanisms in 3D neuronal culture and provide a biological basis for testing new biomaterial-based therapeutics.

*This research was supported in part by a grant to UMBC from the Howard Hughes Medical Institute through the Precollege and Undergraduate Science Education, an Undergraduate Research award from the UMBC Office of Undergraduate Education, NIH-NINDS R01NS065205 (JBL), the Henry-Luce Foundation (JBL), and Wyeth Fellowship at UMBC (AR).