CCB Colloquium presentation by Dr. Vikas Nanda, Rutgers CABM and RWJMS-UMDNJ.
Host: KiBum Lee
Talk Title: "Programmable Self-Assembly of Peptides on Multiple Length Scales"
Abstract: Our group uses computer modeling to address challenges in diverse areas: improving peptide drug pharmacology, developing self-assembling biomaterials and studying protein-based food allergies. Collagen has proven useful as a biomaterial, with applications in wound healing and coating of medical devices. However, natural collagens are difficult to synthesize and costly to extract at safe purity levels from natural sources. We are pursuing computationally designed de novo collagen peptide-based biomaterials, specifying association of individual chains into a collagen triple helix and supermolecular association of triple helices into higher order structures. To make macro-scale fibers and matrices, we need to first successfully engineer individual trimeric units. We designed the sequence of three peptides which assembled into stable A:B:C heterotrimers. These peptides will act as primary modules to direct higher order assembly. Such modules will be combined to build fibers and networks by covalently linking pairs. In such a scenario, the choice of module pairings will direct the nature of the higher order structure.
Structural characterization of a set of computationally designed peptides indicated that heterotrimers were formed. Interestingly, specific mixtures of peptides formed highly regular micrometer length fibers. Models suggested a staggered arrangement of individual chains with 'sticky ends' that polymerized into long fibrils. When fibers aggregated in the test tube, they formed a transparent highly viscous solution. Micro-rheology measurements indicated the solution was an elastic hydrogel, a spongy matrix at ~ 5% weight/volume. Hydrogels are highly useful as the substrate for implants that mediate the controlled release of drugs. We are pursuing new designs that will optimize gellation properties and nanoscale structure.