The Design and Emergent Properties of Supramolecular Peptide-DNA Materials

Natural materials in cells and tissue are composed of a harmony of biomolecules that dynamically organize into vital structures. A simple set of biomolecular building blocks, such as amino acids, oligonucleotides, lipids and monosaccharides, self-organize using covalent and weak, noncovalent interactions into architectures that span nano- to micrometer length scales. While nature is teeming with dynamic multiscale systems, generating such materials synthetically is challenging. In this work, I aim to form life-like materials using design rules from natural self-assemblies.My work focuses on creating synthetic soft materials that have bioinspired hierarchy, referring to the multi-level self-assembly of molecules into nanostructures that further organize into complex morphologies. I use molecular sequences of natural self-assembling biomolecules towards the bottom-up design of hierarchical and stimuli-responsive structures. The systems consist of two classes: (1) peptide-DNA (Chapter 2) or (2) coiled-coil peptide materials (Chapter 3). In the first systems, the secondary structures and mechanical properties of peptide self-assemblies are merged with the predictable, reversible base-pairing of oligonucleotides to generate responsive fibrous scaffolds. Varying single-stranded DNA length within the peptide-DNA molecules drives differences in fiber assembly, and toehold-mediated DNA strand displacement controls reversible fiber bundling. Next, the programmability of DNA is used to create an actin-inspired peptide-DNA crosslinker library with varying lengths, flexibility and valencies to mimic actin-binding proteins in cytoskeletal-like networks. Peptide/peptide-DNA coassemblies yield bundle and spindle networks with DNA-tunable dimensions and mechanics. The structures are then confined within cell-sized droplets to fabricate synthetic cells, where the spatial organization of peptide-DNA, cargo diffusion, and droplet shape change in response to stress are tuned by peptide-DNA design. In Chapter 3, modular dimerizing protein motifs, coiled-coils, are employed to create all-peptide, dynamically-crosslinked materials. These molecules self-assemble into controllable fibers, where small changes in the coiled-coil sequences elicit large changes in fiber growth and monomer exchange kinetics. Multicomponent assemblies result in tunable hierarchical systems that morph in structure and monomer patterning over several days. Pathway selection and changes in coiled-coil sequence vary the time between states as structures evolve, allowing access to a diverse array of life-like architectures.