NIRT: Surface Gradients and the Mechanism of Neuronal Axon Growth

该提案是根据公告NSF 01-157收到的。他们组织了一个纳米级跨学科研究小组（NIRT），其动机是假设理解信号分子浓度梯度在细胞动力学，特别是神经元轴突生长中的作用，具有前所未有的空间分辨率和化学控制是非常重要的。该团队由来自化学、神经科学和机械工程的四名pi组成，他们在表面功能化和生物分子固定化、神经元轴突生长机制以及生物分子的纳米传递和表征工具方面具有专业知识。此次合作的专业知识和协同作用的结合将使他们能够开发出具有以下属性的化学和生化梯度生成方法：(a)梯度支撑在固体表面上，以进行精确控制和量化；(b)梯度具有元胞（~um）和亚元胞（~102 nm）的空间分辨率；(c)任意或“设计”梯度曲线，包括数字（离散）或模拟（连续）梯度，是可能的；(d)该方法不是分子特异性的，梯度可能包括多个组分。提出的方法将基于精确的纳米递送工具，一个容量分辨率为10-18升的电喷雾系统，将化学或生物样品递送到功能化的固体表面上。一个“设计”梯度将由编程的电压脉冲序列与编程的样品运动相结合产生。固体表面的单层组件将被设计用于高分辨率地限制纳米液滴，将信号分子固定在纳米液滴中，并为细胞粘附和生长提供化学或生物相容性。他们计划以神经元为模型生物系统，探索外源分子梯度在引导神经元轴突生长中的作用。这项研究将为参与的学生提供一个极好的机会，在纳米科学/技术的前沿工作，即分子纳米生物学和纳米生物技术。除了研究生培训外，pi计划每年开发并共同教授一门新生研讨会课程，名为“纳米生物学：神经元生长的科学与工程”，以激发本科生的兴趣和参与。预计他们提出的活动将有助于为神经生物学纳米科学及其实际应用的未来创新者和领导者做准备。

This proposal was received in response to the announcement NSF 01-157.They have organized a Nanoscale Interdisciplinary Research Team (NIRT) motivated by the hypothesis that understanding of the roles that concentration gradients of signal molecules play in cell dynamics, neuronal axon growth in particular, with unprecedented spatial resolution andchemical control is very important. The team consists of four PIs from Chemistry, Neuroscience, and Mechanical Engineering, with expertise in surface functionalization and biomolecule immobilization, neuronal axon growth mechanisms, and nano-delivery and characterization tools for biomolecules. The combination of expertise and synergy from this collaboration will allow them to develop methodology for the generation of chemical and biochemical gradients that possess the following attributes: (a) the gradients are supported on a solid surface for precise control and quantification; (b) the gradients possess cellular (~um) and sub-cellular (~102 nm) spatial resolution; (c) arbitrary or "designer" gradient profiles, including digital (discrete) or analog (continuous) gradients, are possible; (d) the method are not molecule-specific and the gradients may include multiple components. The proposed method will be based on a precision nano-delivery tool, an electrospray system capable of 10-18 liter volume resolution, to deliver chemical or biological samples onto a functionalized solid surface. A "designer" gradient will be generated by a programmed voltagepulse-train in combination with programmed movement of the sample. Monolayer assemblies onthe solid surface will be designed to confine the nano-droplet for high resolution, to immobilizesignal molecules in the nano-droplet, and to provide chemical or biological compatibility for celladhesion and growth. They plan to use neurons as a model biological system to explore the roles of gradients of extrinsic molecules in guiding neuronal axon growth.The proposed research will provide an excellent opportunity for participating students to work atone of the forefronts of nanoscience/technology, i.e., molecular nano-biology and nanobiotechnology. In addition to graduate training, the PIs plan to develop and co-teach a freshman seminar course annually on, "Nanobiology: science and engineering of neuron growth," to stimulate undergraduates' interest and participation. It is anticipated that their proposed activities will contribute to the preparation of future innovators and leaders in nanoscience in neurobiology and its practical application.