Immobilization of modular peptides on graphene cocktail for differentiation of human mesenchymal stem cells to hepatic-like cells

Frontiers in Chemistry

Authors:  Behzad Adibi-Motlagh, Ehsan Hashemi, Omid Akhavan, Jafar Khezri, Aram Rezaei, Javad Zamani Amir Zakria, Seyed Davar Siadat, Abbas Sahebghadam Lotfi, Abbas Farmany

Abstract

In this study, two novel biomimetic modular peptide motifs based on the alpha2 subunit of type IV collagen (CO4A2) were designed and immobilized on a graphene platform to imitate integrin and heparan sulfate- (HS-) binding proteins. The in silico study was used to design 9-mer K[KGDRGD]AG and 10-mer KK[SGDRGD]AG for testing designed Integrin-Binding Peptide (dIBP) and HS-Binding Peptide (dHBP). The virtual docking technique was used to optimize the peptide motifs and their relevant receptors. Molecular dynamic (MD) simulation was used to evaluate the stability of peptide-receptor complexes. The effect of the platform on the differentiation of human mesenchymal stem cells (hMSCs) to hepatic-like cells (HLCs) was evaluated. After differentiation, some hepatic cells’ molecular markers such as albumin, AFP, CK-18, and CK-19 were successfully followed. Graphene-heparan sulfate binding peptide (G-HSBP) enhances the mature hepatic markers’ expression instead of control (p ≤ 0.05). The pathological study showed that the designed platform is safe, and no adverse effects were seen till 21 days after implantation.