The overall objective of the integrative research and education career plan is to utilize basic engineering principles (cell mechanics and electrical interfacing technology) and biological principles (neurobiology) to optimize neuronal culturing techniques for examining neuropathological conditions and create a interdisciplinary approach to solving problems and advancing the field of neuroengineering. The initial goal of the research component is to further develop three-dimensional (3-D) cultures of the signaling cells of the brain (neurons) by manipulating the cellular support matrix that surrounds the neurons. The optimized 3-D cell cultures will be used to determine how external physical stimuli (from the physiologic to the pathologic/injury range) are transduced from the support matrix to the cellular organelles. In this controlled system, specific mechanisms of mechanically-initiated cell signals will be sorted out in order to develop cellular thresholds and mechanistically-based pharmacologic interventions. In addition, the introduction of 3-D microelectrodes will be incorporated into the cell cultures for purposes of measuring neuronal activity. Educational efforts will be concurrent with the research activities and stem from the research projects. Undergraduate students will be introduced to problem solving and technological approaches in neurobiological interfacing with microsystems through problem-based learning classes. In addition, the PI will expand a graduate course in bioengineering laboratory principles to modules that can be used for undergraduate research experiences and training of high school science teachers.