(691d) Design and Synthesis of Bioactive Collagen Mimetic Peptides

Peptides, functionally encoded by their amino acid sequence, are increasingly being designed within the biomaterials community for creating mimics of the extracellular matrix found within human tissues. Collagen-like peptides have been designed to mimic parts of the structure and bioactivity of collagen I, the most prevalent protein in the human body and important in the structure and properties of many tissues. Recently, synthesis methods have been developed for self-assembling multifunctional collagen mimetic peptides (mfCMP) for the formation of synthetic matrices with robust and tunable properties. There remains a need for self-assembling peptides with tunable properties inspired by native tissues that can be used to create functional biomaterials with tailorable biophysical and biochemical properties and consistency from batch to batch that have the potential to serve as surrogates for harvested collagen I. To address this need, I have designed and synthesized mfCMPs that contain integrin binding motifs within their amino acid sequence that self-assemble into triple helices and fibrils inspired by natural collagen: e.g., GFOGER (available for binding in intact collagen I) and RGD (available for binding in damaged/denatured collagen I). Triple helix formation is verified by circular dichroism (CD) spectroscopy, and fibril formation is verified by transmission electron microscopy (TEM) and super resolution confocal microscopy. These mfCMPs can be coassembled and incorporated into hydrogel matrices to mimic both healthy and diseased tissue by tuning the number of RGD binding sites. Additionally, I am integrating unique reactive handles for light-triggered crosslinking to further mimic the transition from healthy to diseased tissues. Overall, these mfCMPs are part of a modular system of building blocks that has the potential to be a fully synthetic surrogate for natural collagen I for applications in vitro and in vivo.