Bilingual Biopolymers: Harnessing Dual Information Codes to Control Assembly

Non-technical: This award by the Biomaterials program in the Division of Materials Research to Emory University is for exploration of new biomimetic materials that can be used for applications in the detection of drugs and toxins, or for the controlled delivery of therapeutics. Both nucleic acids and proteins have the ability to encode information and perform specific functions, yet they each benefit from unique advantages with regard to designability and breadth of function. To date, all polymers seeking to mimic these natural biopolymers only take advantage of a single code – either nucleic acid or protein. The proposed work explores novel polymers that are able to simultaneously encode both nucleic acid and protein information, in turn providing greater control over structure and function. Specifically, the research will explore the uptake of these polymer assemblies into cells and their ability to bind and release small molecules such as therapeutics. Additionally, the proposal will explore new modes for controlling structure that mimic those found in nature. This research project will span the fields of materials science, chemistry, and molecular biology, providing undergraduate and graduate students with a highly interdisciplinary training experience involving the use of cutting-edge techniques. This project will also contribute to public scientific literacy through a science communication project implemented in a course taught by the PI, as well as through the PI’s participation as a judge and student mentor for the high school International Science Fair. Technical: The overarching research goal of this NSF proposal is to explore “bilingual biopolymers” as a new class of programmable materials capable of interpreting both peptide and nucleic acid information codes to direct assembly, disassembly, and guest release. Peptide nucleic acid (PNA) serves as an ideal scaffold for these polymers, as it has a peptide-like backbone that can be functionalized with amino acid side chains, and is able to bind sequence-specifically to DNA and RNA. Using prior NSF support, this team generated and characterized “bilingual” PNA sequences having an amphiphilic amino acid code to drive assembly into micelles. They demonstrated stimuli-responsive disassembly in the presence of a complementary DNA or RNA sequence, as well as cell permeability and the ability to sequester hydrophobic guest molecules. Building upon these exciting results, the proposed experiments aim to: (1) Evaluate the effect of side chain structure and pattern on assembly and small-molecule binding capabilities; (2) Investigate the effect of micelle size and surface properties on cellular uptake and small-molecule release; (3) Expand the scope of stimuli-responsive control of assembly via chemically addressable cross-links. The broader impacts of the proposed research include activities aimed at improving undergraduate education and public scientific literacy, and the potential to benefit public health through the development of improved diagnostics and drug delivery platforms. 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.