NIRT: Surface Gradients and the Mechanism of Neuronal Axon Growth

他们组织了一个纳米尺度跨学科研究团队(NIRT)，其动机是理解信号分子的浓度梯度在细胞动力学中所起的作用，特别是神经元轴突的生长，具有前所未有的空间分辨率和化学控制。该团队由来自化学、神经科学和机械工程的四名PI组成，他们拥有表面功能化和生物分子固定、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的专业知识。这次合作的专门知识和协同作用将使他们能够开发产生化学和生化梯度的方法，这些方法具有下列特点：(A)梯度以固体表面为载体，用于精确控制和定量；(B)梯度具有细胞(~um)和亚细胞(~102 nm)的空间分辨率；(C)可能有任意或“设计者”的梯度轮廓，包括数字(离散)或模拟(连续)梯度；(D)该方法不是分子特有的，梯度可包括多种成分。所提出的方法将基于一种精密的纳米输送工具，即一种能够达到10-18升体积分辨率的电喷雾系统，将化学或生物样品输送到功能化的固体表面。通过编程的电压脉冲串与编程的样品移动相结合，将产生“设计者”的梯度。固体表面的单层组件将被设计成限制纳米液滴以实现高分辨率，固定纳米液滴中的信号分子，并为细胞黏附和生长提供化学或生物兼容性。他们计划使用神经元作为模型生物系统，探索外在分子的梯度在引导神经元轴突生长中的作用。拟议的研究将为参与研究的学生提供一个极好的机会，让他们在纳米科学/技术的前沿之一工作，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，主题为“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。预计他们拟议的活动将有助于培养神经生物学及其实际应用领域未来纳米科学的创新者和领导者。

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.