Dr. Ronit Freeman
Simpson Querrey Institute for BioNanotechnology, Feinberg School of Medicine
Northwestern University, Chicago, IL 60611, US
The native extracellular matrix is a space in which signals can be displayed dynamically and reversibly, positioned with nanoscale precision, and combined synergistically to control cell function. Artificial forms of this matrix for tissue regeneration need to recapitulate these three characteristics in a single molecular platform. Most efforts in this area have effectively addressed only one of these three key phenomena, and focused mainly on static cell adhesion or irreversible switching of bioactivity. This talk will describe a molecular platform based on peptide-DNA conjugates 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 complementary 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, without the need for external stimuli like photons or electrochemical potentials. The DNA was also used as a molecular ruler to control the distance-dependent synergy between two adhesion peptides. Finally, orthogonal DNA handles were designed to allow for the selective presentation of different signals, with the ability to independently up- or down-regulate each over time. This enabled us to discover that neural stem cells organized as neurospheres derived from murine spinal cord can be triggered to migrate out in response to an exogenous signal, and then driven to regroup into a neurosphere as the signal is removed.
This talk will also demonstrate the formation of one-dimensional assemblies of peptide-DNA hybrids with filamentous architecture and three-dimensional hydrogel networks based on DNA-peptide amphiphiles that mimic the structure and function of the natural extracellular environment. These novel constructs will enable to elucidate how external cues direct cell behavior and orchestrate cellular processes, which may have great importance for mimicking in vivo tissue remodeling and dynamics.