Summary: My research program focuses on the design, synthesis and characterization of functional supramolecular biomaterials based on the self-assembly of peptides and peptide-polymer conjugates and how to use these materials to probe and precisely control various biological processes.
Fundamentally we aim to understand how multiple non-covalent interactions influence the self-assembly process and how to gain structural control across multiple length scales down to the molecular level. We are also interested in exploring how biological systems “sense” the dynamics of these materials and how the supramolecular assembly influences various cellular processes, such as receptor targeting, intracellular trafficking and proton transport. The following research description reflects our current efforts to tackle some of the critical biomedical challenges through novel supramolecular biomaterials.
Project 1: Membrane-Active Biomaterials
Membrane-active materials play important roles toward development of novel and more effective antimicrobial and anticancer therapy. They function by interacting with the cell membrane to cause membrane disruption or direct translocation for cargo delivery. Our group reported a library of membrane-active nanofibers based on the self-assembly of beta-sheet forming peptides. Upon self-assembly, supramolecular ionic clusters are displayed on the rigid nanofiber backbone and their conformational flexibility can be further tuned to enhance the membrane activity. These nanofibers demonstrate great potential as broad-spectrum antimicrobial materials and cell penetrating materials for the delivery of a range of therapeutics.
Project 2. Microenvironment Triggered Supramolecular Biomaterials
We developed a toolbox of integrated multidomain peptides (MDPs) that can respond to various biological cues, such as different pH gradient, reductive microenvironment, and enzyme to form smart, microenvironment triggered supramolecular assemblies. The proof-of-concept for this novel design was demonstrated using reduction as a trigger to form supramolecular nanofibers for targeted imaging of brain tumor cells. Overall, the approach is highly adaptable and transformative for the design and synthesis of supramolecular biomaterials to target various diseases, not limited to cancer.
Project 3: Shape-specific Nanostructured Protein Mimics from De Novo Designed Chimeric Peptides
The ability to build artificial proteins represents an important step toward the goal of creating artificial life. My group developed a new methodology for the construction of symmetry controlled self-assembling artificial proteins. We demonstrated the self-assembly of well-defined tetrahedral dodecamers and trigonal bipyramidal hexamers using chimeric peptides as the molecular building blocks. We will continue refining the fundamental structure as well as exploring their therapeutic potential for targeted molecular imaging and therapy using different peptide or carbohydrate ligands.
