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Immobilization of Modular Peptides on Graphene Cocktail for Differentiation of Human Mesenchymal Stem Cells to Hepatic-Like Cells Publisher



Adibimotlagh B1, 2 ; Hashemi E1, 3 ; Akhavan O4, 5 ; Khezri J1 ; Rezaei A6 ; Zamani Amir Zakria J1 ; Siadat SD7 ; Sahebghadam Lotfi A2 ; Farmany A8, 9
Authors
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Authors Affiliations
  1. 1. National Research Center for Transgenic Mouse, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
  2. 2. Department of Clinical Biochemistry, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran
  3. 3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Physics, Sharif University of Technology, Tehran, Iran
  5. 5. Institute for Nanoscience and Nanotechnology, Sharif University of Technology, Tehran, Iran
  6. 6. Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
  7. 7. Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran
  8. 8. Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
  9. 9. Dental Implant Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

Source: Frontiers in Chemistry Published:2022


Abstract

In this study, two novel biomimetic modular peptide motifs based on the 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). 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. Copyright © 2022 Adibi-Motlagh, Hashemi, Akhavan, Khezri, Rezaei, Zamani Amir Zakria, Siadat, Sahebghadam Lotfi and Farmany.
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