NSF/DMR-BSF: Synergistic biopolymer co-assembly regulating the emergence of translation and replication in synthetic networks

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Part 1. Non-Technical SummaryLife has been broadly conceptualized as a computation optimizing the storage and use of information to enable evolution. On Earth, life exploits polymer cooperativity, coupling “digital” information storage in DNA with an environmentally responsive “analog” function of proteins. Such cooperativity is achieved through the digital-to-analog converter (DAC) of molecular information flow known as the ribosome. Based on current synthetic capabilities for preparing and modifying polymers, the goal of this proposal is to extend life’s mutualistic polymer networks to achieve alternative replication and synthetic translation, extending the computations beyond existing biopolymers. Conceptually, achieving this goal would change our understanding of life in the Universe by moving evolvable materials beyond biopolymers, generating functional materials both orthogonal to and compatible with current biological networks, and revealing new opportunities for identifying life beyond Earth. Achieving these goals have the potential to train a new generation of material scientists, scholars who naturally bridge the worlds of synthetic, alternative, and natural biomaterials, capturing the imagination of scholars and the lay public with the potential applications for chemical evolution outside of extant biology on this planet and beyond.Part 2. Technical SummaryBuilding on the practical success of block copolymers and polymer blends, the emerging energetic codes for self- and co-assembly of biopolymers, and the synthetic and analytical tools allowing for the characterization of mixtures of complex polymers, it now becomes possible to explore reaction-diffusion polymerization networks that cooperatively drive physical phase changes. Such oligomerization networks can reach critical Flory-Huggins thresholds to drive liquid-liquid phase separation. The resulting solute rich phases create new reaction environments that change reaction kinetics. This progressive tension, coupling dynamic physical phases with altered reaction networks, will be used to create self-organizing networks. As the solute-rich phases grow via Ostwald’s rule of stages, seeding diverse ordered populations of nuclei that access liquid-solid phase changes at specific particle sizes, the new phase becomes capable of autocatalytic propagation of a paracrystalline surface able to template new polymer growth. An autocatalytic feedback loop will appear if the new polymer is engineered to template the initial assembly. This proposal will compare two systems to exploit this dynamic physical/chemical tension -- a covalently connected peptide-nucleic acid chimera and separate peptide/nucleic acid co-assemblies, specifically under conditions where each templates the other’s oligomerization intermolecularly. These two complementary approaches to translation are designed to model a minimal ribosome. The work will take advantage of the synergistic and complementary strengths in the collaborating laboratories, the necessary structural and kinetic analyses of these catalytic assemblies. Nature’s ribosome achieves unidirectional polymer translation, nucleic acid to protein. The proposed minimal synthetic system will be a coacervate catalyzing dynamic reaction cycles of cross-templating oligomers and provide a critical proof-of-principle for defining the general rules limiting polymer to polymer translation. This minimal system approach has the potential ultimately to extend to other materials for evolving desired function as controlled by environmental inputs. If successful, this approach will add a critical new strategy for molecular computing and discovering novel functional materials.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.