(39c) Peptide-DNA Hybrid Nanomaterials for Biology and Medicine

Peptides and DNA represent two of the most attractive categories of molecules for the construction of nanomaterials for biology and medicine. Peptides provide a rich palette of biological functionality and self-assembly behavior, and DNA can be used to construct complex nanostructures with programmable, dynamic properties. We sought to merge the advantages of these two molecular platforms through the use of peptide-DNA (P-DNA) hybrid materials. I will present recent progress in various areas: 1) Peptide-DNA nanotubes for guiding stem cell differentiation. We conjugated the cell adhesion peptide RGDS to single-stranded DNA, and used this hybrid molecule to construct DNA tile-based nanotubes displaying the peptide in a multivalent fashion. The nanotubes served as an efficient scaffold for neural stem cell adhesion and differentiation (NSCs). 2) Dynamic and programmable control of cell bioactivity: I will describe a unified molecular platform that can be programmed to control the dynamics, spatial positioning, and combinatorial synergies of signals in extracellular matrices. In this approach, a peptide-DNA (P-DNA) molecule is immobilized on a surface through DNA tethers. By engineering a series of tethers responsive to different stimuli, we show that cells adhered and spread on the surface reversibly. The use of P-DNA in cell signaling allowed multiple cycles of reversibility by simply adding soluble biologically compatible molecules such as DNA and enzymes. The DNA was also used as a molecular ruler to control the distance-dependent synergy between two adhesion peptides. Finally, orthogonal DNA tethers combined the binding of both a peptide and a bioactive protein to the surface in order to enhance cell differentiation. Multiple orthogonal DNA handles can be designed to allow for the selective presentation of different signals, with the ability to independently up- or down-regulate each over time. 3) Peptide amphiphile (PA)-DNA conjugates for programmable hydrogels. Peptide amphiphiles (PAs) consist of peptides bearing hydrophobic tails that allow their self-assembly into one-dimensional nanofibers ~10 nm in diameter and microns in length. These nanofibers can be used to construct highly potent bioactive hydrogels by incorporating functional epitopes. We synthesized PA-DNA molecules which, upon co-assembly with unmodified PAs, result in hybrid nanofibers that display multivalent DNA handles. The DNA can be used to reversibly crosslink the fibers into self-supporting gels, dynamically and reversibly present biological signals, or tune the mechanical properties of the resulting materials.