Developing self-assembly methods to arrange individual molecules and atoms precisely in space and time represents a powerful approach for creating new materials that can unlock future technology. This emerging concept of "growing materials" from the bottom-up provides the intellectual underpinning that motivates research within the Merg lab. Specifically, we are interested in developing synthetic methods for constructing unexplored peptide building block designs for creating hierarchical 2D and 3D architectures with tailorable physical and chemical properties - an outstanding challenge within the field of molecular self-assembly.
A common thread within the lab centers around employing peptides and synthetically modified peptide conjugates as fully synthetic biomolecular building blocks. Peptides represent an attractive biomacromolecular building block because of the ability to encode a large amount of structural, chemical, and functional information within the sequence architecture (as evidenced by the exquisite sequence-to-structure-to-function relationship exhibited by proteins). Furthermore, the high-information content of peptides and their conjugates can be programmed and postsynthetically modified using a range of chemical synthesis techniques, including solid-phase peptide synthesis (SPPS) and bioconjugation. The Merg lab is invested in designing and synthesizing new classes of hybrid, multivalent peptide-based building blocks as a means to i) tap into unexplored peptide assembly spaces (e.g., fabrication of porous 2D and 3D architectures); ii) broaden the utility and capabilities of peptide-based materials; and iii) create biomaterials that can be tuned physically and chemically across the nano- to microscale.
FOUR RESEARCH THRUSTS:
- Research Thrust 1: "Peptide Origami" Assembly Strategy for Constructing Fully Synthetic Protein Polyhedra
Protein-based nanocages have potential widespread utility as protein stabilizers, immunoisolation capsules, nanoscale reactors/artificial enzymes, and as therapeutic and theranostic delivery agents, where functional cargo can be loaded within the cage. Furthermore, these architecturally defined structures can be employed as 3D supramolecular building units for the fabrication of porous hiearchical assemblies (e.g., protein-MOFs). While materials chemists have been highly successful in assembling extended structures from peptides subunits, the construction of discrete 3D peptide-based assemblies has only recently been explored. Research within this thrust is focused on developing a new class of cyclic peptide tiles (coiled coil peptide tiles; CCPTs) that are designed to assemble and fold into 3D nanoscale polyhedra using a "peptide origami-based" strategy.
- Research Thrust 2: DNA Nanostructure-Mediated Imprinting onto 2D Biomaterial Templates
DNA origami has emerged as a powerful method for assembling intricate, designable nanostructures. It is unrivaled by alternative bottom-up assembly methods that employ other various molecular building blocks (e.g., peptides, polymers, proteins). However, a significant limitation of nucleic acid-based assemblies is that they do not confer the same degree of chemical and biological functionality compared to peptide/protein-based assemblies. Within this research thrust, we aim to employ DNA nanostructures as nanoscale templates for imprinting/patterning the surface of peptide-based materials. Such ability to spatially and chemically modify the exterior of nanomaterials would dramatically broaden the application scope and capabilities of peptide/protein-based biomaterials. Developing methods to organize matter with nanoscale resolution is an important step for revolutionalizing the field of bionanotechnology (e.g., scaffolding for catalytic and sensing applications, bionanoelectronics, and contruction of hierarchical assemblies).
- Research Thrust 3: Living Crystallization-Driven Self-Assembly (CDSA) of Peptide Nanomaterials using "Molecular Seeds"
Seeded growth assembly of crystallizable sequence-defined (bio)polymer bulding blocks holds immense promise for the design and preparation of complex and well-defined nanoscale architectures. A vast majority of self-assembly methods employ a "dissolve and wait" approach, which afford limited control over the physical dimensions of the assembled materials and frequently yield non-uniform assembly products. To realize the potential of incorporating nanoscale materials (and there potential applications) into future technological devices, it is imperative to develop methods to reliably predict and tailor nanoscale materials that are self-assembled from the bottom-up. With this in mind, we are actively pursuing and developing "living" CDSA methods that employ molecularly designed and synthesized seeds that serve as pre-made nucleation sites. These pre-maded nucleation sites will serve as seeds for the controlled epitaxial growth of free crystallizable monomers to yields. By bypassing the nucleation events, which are difficult to control and is a main contributor to assembly polydispersity, we aim to better control the physical, chemical, and ultimately functional properties of self-assembled materials.
- Research Thrust 4: Nanoparticle Superlattices Assembled via Protein-Mediated Interactions
The rational construction of nanoparticle superlattices using DNA hybridization has emerged as a powerful assembly method for constructing designer crystals from the bottom-up. These micro- and macroscopic materials, composed of individual DNA-functionalized nanoparticles (considered “programmable atom equivalents”), represent the emergent idea of repurposing biological molecules for constructing synthetic materials. In a similar manner, our group is interested in employing protein-mediated interactions to create analogous nanoparticle superlattices. While protein-based interactions are more complex and challenging compared to the straightforward base-pairing rules of DNA, the development of utilizing a more functionally and chemically diverse interaction portends well to creating materials that can more seamlessly integrate with biological systems. The development of these bio-inorganic materials would have potential biomedical applications as biological sensors and as functional components of biomedical devices and implants.