Polymers are pervasive in society – from plastic bottles to fingerprint resistant coatings on cell-phone screens, these materials are a critical component of global technological, medical, and environmental advances. Despite this ubiquity, many polymers are currently designed and analyzed with only one specific application in mind. It can take years to identify an existing polymer that would be appropriate for use in a different application, especially if the chemical and physical properties required for the new application are unknown. To help match polymer materials to new applications, this proposal describes a synthetic platform that will enable hundreds of thousands of materials to be screened simultaneously – a scale orders of magnitude above current strategies for synthetic polymers and rivaling technologies like Nobel prize-winning directed evolution. To facilitate high throughput polymer screening, DNA will be used as a staple to bring together multiple polymer blocks. The modular assembly strategy allows for few synthetic pieces to lead to large libraries of hybrid block copolymers. The DNA staples have also been designed to carry identifying information that can help decode which polymer blocks have been stapled together, even in complicated mixtures. Once polymer blocks have been stapled together, the resulting hybrid materials can be screened for desirable properties (such as the ability to shield proteins from harsh environments, which is useful for stabilizing protein-based drugs like insulin), then isolated and identified using DNA sequencing strategies. This project requires interdisciplinary inspiration and techniques, which is an aspect of scientific achievements that is frequently overlooked in the classroom. To address this disconnect, two education programs building on current successful frameworks are proposed: (1) BioInspiring – on-site and virtual activities connecting biology-inspired science to every-day items and (2) Sci-athonU – a collaborative student competition to generate interdisciplinary research proposals that target global challenges. The objective of these educational programs is to increase access to STEM resources that highlight communication and collaboration as critical elements of science. This proposed research program has the long terms goals of revealing design principles for polymers with sophisticated functions to advance national medical, technological, and environmental goals, while providing novel approaches to increasing the motivation and retention of students from groups historically underrepresented in STEM.
Decodable polymer libraries have the potential to revolutionize the identification of structure-function relationships for synthetic macromolecules. While the protein data bank (PDB) contains structural information for almost 50,000 distinct proteins, there are significantly fewer characterized materials within the diverse structure space of synthetic macromolecules, leaving the identification of structure-function relationships in its infancy. High-throughput experimentation has had a revolutionary impact on biochemistry with RNA seq revealing real-time quantitation of protein expression and directed evolution yielding unique protein structure-function relationships. Despite the impact of these powerful combinatorial approaches, high-throughput experimentation with synthetic polymers remains rare. With current techniques, each polymer must be characterized in parallel, as there is currently no strategy for the rapid identification of polymers isolated from a mixture. Motivated by this fundamental gap, this work aims to use DNA “staples†that encode the polymer composition throughout a block copolymer and to provide proof-of-principle high-throughput assays characterizing polymer morphology and protein stabilization. Synthetic strategies are proposed for the design of linear, brush, and star-like polymer morphologies assembled with strategically designed architectures, and sequencing protocols are proposed to identify isolated polymers. The ultimate goal of this proposal is to provide a platform that expands the capabilities of polymer characterization from hundreds to thousands of polymers in a single experiment, enabling rapid identification of novel relationships between polymer structure and advanced functions.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
