Neuronal Biointerface: Micropatterned Lipid Bilayers

描述(申请人提供)：许多对神经功能至关重要的细胞功能，从调节突触强度到神经元迁移和寻路，都是由细胞外环境中生物分子在空间上的复杂和动态排列所驱动的。了解这些因素在正常和病理条件下的影响，对于神经功能障碍的治疗和损伤后这些组织的修复具有重要意义。推动这一提议的概念是，在实验表面捕捉这种复杂性并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。这项提案的技术目标是响应神经技术研究、开发和增强PA，开发一个结合细胞间通讯蛋白质的平台，通过使用支持的脂类双层来保持这些蛋白质的横向迁移性，进入这样的微图案化系统。我们的目标是达到空间分辨率和精确度，在这些蛋白质的呈现可与体内观察到的。具体地说，这些拟议的研究努力捕捉玻璃盖片上的神经元间突触，实际上创造了一个改进的神经元-基质生物界面。作为这一方向的第一步，这项提议将检查连接到支持的脂质双层的突触后蛋白Neuroigin-1在与平面支持相互作用的神经元中促进突触前复合体组装的能力。该系统还应广泛应用于更大规模的细胞-细胞相互作用的研究，如星形胶质细胞-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.