title: Cell Adhesion Induced Using Surface Modification with Cell-Penetrating Peptide-Conjugated Poly(ethylene glycol)-Lipid: A New Cell Glue for 3D Cell-Based Structures.
abstract: We synthesized a novel material, cell-penetrating peptide-conjugated poly(ethylene glycol)-lipid (CPP-PEG-lipid), that can induce the adhesion of floating cells. Firm cell adhesion with spreading could be induced by cell surface modification with the CPP-PEG-lipids. Cell adhesion was induced by CPPs but not by any other cationic short peptides we tested. Here, we demonstrated adherence using the floating cell line CCRF-CEM as well as primary human T cells, B cells, erythrocytes, and hepatocytes. As compared to cells grown in suspension, adherent cells were more rapidly induced to attach to substrates with the cell-surface modification. The critical factor for attachment was localization of CPPs at the cell membrane by PEG-lipids with PEG > 20 kDa. These cationic CPPs on PEG chains were able to interact with substrate surfaces such as polystyrene (PS) surfaces, glass surfaces, and PS microfibers that are negatively charged, inducing firm cell adhesion and cell spreading. Also, as opposed to normal cationic peptides that interact strongly with cell membranes, CPPs were less interactive with the cell surfaces because of their cell-penetrating property, making them more available for adhering cells to the substrate surface. No effects on cell viability or cell proliferation were observed after the induction of cell adhesion. With this technique, cells could be easily immobilized onto PS microfibers, an important step in fabricating 3D cell-based structures. Cells immobilized onto 3D PS microfibers were alive, and human hepatocytes showed normal production of urea and albumin on the microfibers. This method is novel in inducing firm cell adhesion via a one-step treatment.
authors.affiliation: Department of Bioengineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.|Department of Immunology, Genetics, and Pathology (IGP), Uppsala University , Dag Hammarskjölds väg 20, SE-751 85 Uppsala, Sweden.
authors.forename: Yuji
authors.identifier: 0000-0002-0709-1000
authors.initials: Y
authors.lastname: Teramura
authors.affiliation: Department of Immunology, Genetics, and Pathology (IGP), Uppsala University , Dag Hammarskjölds väg 20, SE-751 85 Uppsala, Sweden.
authors.forename: Sana
authors.initials: S
authors.lastname: Asif
authors.affiliation: Department of Immunology, Genetics, and Pathology (IGP), Uppsala University , Dag Hammarskjölds väg 20, SE-751 85 Uppsala, Sweden.|Linnæus Center of Biomaterials Chemistry, Linnæus University , SE-391 82 Kalmar, Sweden.
authors.forename: Kristina N
authors.initials: KN
authors.lastname: Ekdahl
authors.affiliation: Department of Women's and Children's Health, Uppsala University Hospital , SE-751 85 Uppsala, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Gustafson
authors.affiliation: Department of Immunology, Genetics, and Pathology (IGP), Uppsala University , Dag Hammarskjölds väg 20, SE-751 85 Uppsala, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
keywords: 3D structure; cell adhesion; cell surface modification; cell-penetrating peptide (CPP); poly(ethylene glycol)-conjugated phospholipid (PEG−lipid)