(6gj) Instructing cell bioactivity using programmable DNA-peptide hybrid materials

DNA is one of the most promising molecules for the construction of nanomaterials, with programmable control over both nanostructure and dynamics. Despite this potential, DNA has not been used to a great extent in supramolecular biomaterials for regenerative medicine. My research uses novel DNA-peptide hybrids to create scaffolds for instructing cell behavior in ways not possible with current materials. I will present work on two main projects. The first uses a DNA nanotube as a scaffold for neural stem cell (NSC) attachment and directed differentiation. Modifying one of the strands that comprises the nanotube with a cell adhesion peptide results in a multivalent display of the biological signal on the nanotube surface. These nanotubes are potent scaffolds for NSC attachment compared with unmodified nanotubes, and selectively promote their differentiation to neurons. DNA allows for rational control over the structure obtained, and if nanotube formation is prevented, the NSCs no longer differentiation into neurons. My second project uses DNA as a handle to endow a biologically inert polymeric surface with bioactivity. DNA handles on an alginate coating allow for immobilization of peptides that promote fibroblast adhesion and spreading. By dynamically removing the peptide signal (using several DNA-specific triggers), it is possible to programmably reverse this bioactivity. DNA can also serve as a scaffold to present multiple signals with nanoscale control, promoting a distance-dependent synergy between two bioactive peptides or a peptide and a growth factor. These two projects highlight the power of DNA in both controlling nanostructure and dynamic properties of a cell scaffold, and are the foundation for a new area of DNA-biomolecule scaffolds for regenerative medicine.