NIRT: Surface Gradients and the Mechanism of Neuronal Axon Growth

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 and

chemical 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 voltage

pulse-train in combination with programmed movement of the sample. Monolayer assemblies on

the solid surface will be designed to confine the nano-droplet for high resolution, to immobilize

signal molecules in the nano-droplet, and to provide chemical or biological compatibility for cell

adhesion 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 at

one 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.