Recombinant Collagen-Like Protein and Hyaluronic Acid Hybrid Gels Mimic Pancreatic Cancer Extracellular Matrix Environment

Collagen fibers form highways along which cancer cells migrate. Pancreatic cancer (PC) is currently the fourth leading cause of death due to its particularly dense surrounding microenvironment comprised of collagen, hyaluronic acid, and various basement membrane proteins. PC cells migrate along collagen homotrimeric collagen chains. We have produced blank-slate collagen based on <i>Streptococcal </i>collagen-like 2.28 (Scl2.28) protein grown in <i>E. Coli</i>. A minimal sequence has been obtained to create a collagen triple helix without motifs recognized by mammalian cells. Existing collagen-like protein (CLP) materials require high concentration or freeze-drying techniques which may denature the triple helix structure. Here, our CLP has been covalently attached to norbornene functionalized hyaluronic acid (NorHA). This novel CLP-NorHA material provides a tuneable microenvironment in which to study heterotypic pancreatic cancer and other stroma-rich cancers (such as prostate, liver, and breast). Reproducible fabrication of viscoelastic hydrogels that mimic the architecture of natural matrices will prove useful in recreating tumor microenvironment in vitro for disease modelling and drug development.