In this award funded by the Macromolecular, Supramolecular, and Nanochemistry Program, Drs. Thomas Beebe, Joseph Fox (both from the University of Delaware) and Ryan Mehl of Oregon State University will develop a novel method for the creation of spatial patterns, including gradients, of biological molecules on surfaces. The approach utilizes the tetrazine ligation, an extremely rapid bioorthogonal reaction developed by Dr. Fox. The essential novel component of the proposed program is the ability to control the presentation of proteins that are attached to a surface. This will be achieved using a method developed by Dr. Mehl, in which tetrazine-containing unnatural amino acids are site-specifically displayed at surface-exposed positions in proteins. Putting these two elements together results in the ability to create micrometer to centimeter patterns and gradients using microcontact printing of the clickable trans-cyclooctene on the surface, followed by reaction with tetrazine-modified proteins and protein domains. The three main objectives of this proposal are: (a) synthesis and characterization of gradients and patterns of immobilized proteins on surfaces, starting from trans-cyclooctene; (b) development of methods for photochemically patterning surfaces; (c) permissive substrates for neuron guidance with oriented fibronectin domains.
All of the award's objectives make use of the novel element of controlled protein presentation. Since many emerging biotechnologies rely on the attachment of biomolecules to surfaces, preferably in a bioactive state, this project can greatly enhance detection limits, readout speed, shelf-life, and general functionality of these emerging technologies.
This award features an education and outreach plan involving high school students, their teachers, undergraduate students, graduate students and postdoctoral researchers, all working together between three different research groups using organic synthesis, surface chemistry and analysis, and bioorganic chemistry at the University of Delaware and at Oregon State University. This award will also support outreach efforts to a local African-American high school teacher, Ms. Loraine Snead of Wilmington Friends School. Ms. Snead has developed a high school curriculum that teaches students modern analytical and spectroscopic techniques. Over the past 3 years, Dr. Fox has worked with Ms. Snead to support her curricular innovations.