Neuronal Biointerface: Micropatterned Lipid Bilayers

描述（由申请人提供）：从突触强度的调节到神经元迁移和寻路，对神经功能至关重要的广泛的细胞功能由细胞外环境中生物分子的空间复杂和动态排列驱动。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。驱动这一提议的概念是，在实验表面上捕获这种复杂性以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。该提案的技术目标是响应神经技术研究、开发和增强PA，开发一种平台，该平台将细胞-细胞通信蛋白结合到这种微图案化系统中，通过使用支持的脂质双层来保留这些蛋白质的横向移动性。我们的目标是实现空间分辨率和精度在这些蛋白质的介绍，在体内观察到的。具体而言，这些拟议的研究努力在盖玻片上捕获神经元间突触，实际上，创建改进的神经元-基底生物界面。作为在这个方向上的第一步，该建议将检查突触后蛋白Neuroligin-1的能力，栓系到支持的脂质双层，以促进组装的突触前复合物与平面支持相互作用的神经元。该系统也可广泛应用于大规模细胞-细胞相互作用的研究，例如星形胶质细胞-神经元信号传导对神经元迁移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.