AUTHOR=Adibi-Motlagh Behzad , Hashemi Ehsan , Akhavan Omid , Khezri Jafar , Rezaei Aram , Zamani Amir Zakria Javad , Siadat Seyed Davar , Sahebghadam Lotfi Abbas , Farmany Abbas TITLE=Immobilization of modular peptides on graphene cocktail for differentiation of human mesenchymal stem cells to hepatic-like cells JOURNAL=Frontiers in Chemistry VOLUME=Volume 10 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.943003 DOI=10.3389/fchem.2022.943003 ISSN=2296-2646 ABSTRACT=In this paper, two novel biomimetic modular peptide motifs based on alpha-2 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). 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 platform on human mesenchymal stem cells (hMSCs) differentiation 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. It was shown that graphene-heparan sulfate binding peptide (G-HSBP) enhances the mature hepatic markers expression instead of control (p≤0.05). Pathological study showed that the designed platform is safe and no adverse effect was seen till 21 days after implantation.