Neuronal Biointerface: Micropatterned Lipid Bilayers

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DESCRIPTION (provided by applicant): A wide range of cellular functions critical to neural function, from modulation of synaptic strength to neuronal migration and pathfinding, are driven by the spatially complex and dynamic arrangement of biomolecules in the extracellular environment. Understanding the influence of these factors under both normal and pathological conditions is valuable to the treatment of neurological disorders and repair of these tissues following injury. The concept driving this proposal is that capturing this complexity on an experimental surface for presentation to cells in model systems is an important bridge between cellular and molecular level studies of neural function. The technical goal of this proposal, in response to a Neurotechnology Research, Development, and Enhancement PA, is to develop a platform that incorporates cell-cell communication proteins, retaining the lateral mobility of these proteins through the use of supported lipid bilayers, into such micropatterned systems. The goal is to achieve spatial resolution and precision in the presentation of these proteins comparable to that observed in vivo. Specifically, these proposed studies strive to capture the interneuronal synapse on a glass coverslip, in effect, create an improved neuron-substrate biointerface. As a first step in this direction, this proposal will examine the ability of the post-synaptic protein Neuroligin-1, tethered to a supported lipid bilayer, to promote assembly of presynpatic complexes in neurons interacting with the planar support. This system should also be widely applicable for the study of larger-scale cell-cell interactions, such as the influence of astrocyte-neuron signaling in neuron migration and the influence of the cell microenvironment on stem cell function.