Unraveling the role of integrating signal peptides into natural collagen on modulating cancer cell adhesion.

Abstract

The signal peptides GVMGFO and GFOGER exhibit differential binding affinities towards Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and HT-1080 human fibrosarcoma cells, respectively, which in turn modulate the cell adhesion properties of natural collagen. GVMGFO demonstrates a more potent interaction with discoidin domain receptor 1(DDR1)-expressing MCF-7 cells, whereas GFOGER preferentially binds to the integrin α2β1 present on HT-1080 cells. The integration of GVMGFO into natural collagen through direct doping or crosslinking markedly enhances its association with MCF-7 cells, especially when optimal peptide concentrations and blending ratios are utilized, indicating a synergistic effect. This augmented adhesion is attributed to specific binding at the DDR1-collagen interface, facilitated by a constellation of amino acids within the collagen scaffold engaging with the DDR1 discoidin (DS) domain through polar interactions and hydrogen bonding. Conversely, the incorporation of GFOGER into natural collagen through co-assembling or crosslinking leads to a progressive increase in adherence to HT-1080 cells, as evidenced by the peptide's affinity for integrin α2β1. These findings advance the design of collagen-based biomaterials for targeted cellular interactions in the medical, pharmaceutical, and enhance our understanding of the molecular mechanisms governing peptide-collagen mediated cell adhesion processes.