Neuronal Biointerface: Micropatterned Lipid Bilayers

描述（由申请人提供）：从突触强度调节到神经元迁移和寻路，对神经功能至关重要的广泛细胞功能是由细胞外环境中生物分子的空间复杂和动态排列驱动的。了解这些因素在正常和病理条件下的影响对神经系统疾病的治疗和损伤后这些组织的修复是有价值的。推动这一提议的概念是，在实验表面上捕获这种复杂性并将其呈现给模型系统中的细胞是神经功能的细胞和分子水平研究之间的重要桥梁。作为对神经技术研究、开发和增强PA的回应，该提案的技术目标是开发一个整合细胞-细胞通讯蛋白的平台，通过使用支持的脂质双分子层来保持这些蛋白的横向流动性，进入这种微模式系统。目标是在这些蛋白质的呈现中达到与在体内观察到的相当的空间分辨率和精度。具体来说，这些拟议的研究努力捕捉玻璃盖上的神经元间突触，实际上，创造了一个改进的神经元-基质生物界面。作为这个方向的第一步，本研究将研究突触后蛋白Neuroligin-1与支持的脂质双分子层连接的能力，以促进与平面支持相互作用的神经元中突触前复合物的组装。该系统也应广泛适用于更大规模的细胞-细胞相互作用的研究，如星形细胞-神经元信号在神经元迁移中的影响以及细胞微环境对干细胞功能的影响。

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.