Browsing by Author "Gunay, Gokhan"
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Item Open Access Antigenic GM3 lactone mimetic molecule integrated mannosylated glycopeptide nanofibers for the activation and maturation of dendritic cells(American Chemical Society, 2017) Gunay, Gokhan; Ekiz, Melis Sardan; Ferhati, X.; Richichi, B.; Nativi, C.; Tekinay, Ayse B.; Güler, Mustafa O.The ability of dendritic cells to coordinate innate and adaptive immune responses makes them essential targets for vaccination strategies. Presentation of specific antigens by dendritic cells is required for the activation of the immune system against many pathogens and tumors, and nanoscale materials can be functionalized for active targeting of dendritic cells. In this work, we integrated an immunogenic, carbohydrate melanoma-associated antigen-mimetic GM3-lactone molecule into mannosylated peptide amphiphile nanofibers to target dendritic cells through DC-SIGN receptor. Based on morphological and functional analyses, when dendritic cells were treated with peptide nanofiber carriers, they showed significant increase in antigen internalization and a corresponding increase in the surface expression of the activation and maturation markers CD86, CD83 and HLA-DR, in addition to exhibiting a general morphology consistent with dendritic cell maturation. These results indicate that mannosylated peptide amphiphile nanofiber carriers are promising candidates to target dendritic cells for antigen delivery. © 2017 American Chemical Society.Item Open Access A modular antigen presenting peptide/oligonucleotide nanostructure platform for inducing potent immune response(Wiley - VCH Verlag GmbH & Co. KGaA, 2017-05) Tohumeken, Sehmus; Gunduz, Nuray; Demircan, M. Burak; Gunay, Gokhan; Topal, Ahmet E.; Khalily, M. Aref; Tekinay, T.; Dana, Aykutlu; Güler, Mustafa O.; Tekinay, Ayse B.The design and development of vaccines, which can induce cellular immunity, particularly CD8+ T cells hold great importance since these cells play crucial roles against cancers and viral infections. Covalent conjugation of antigen and adjuvant molecules has been used for successful promotion of immunogenicity in subunit vaccines; however, the stimulation of the CD8+ T‐cell responses by this approach has so far been limited. This study demonstrates a modular system based on noncovalent attachment of biotinylated antigen to a hybrid nanofiber system consisting of biotinylated self‐assembling peptide and CpG oligodeoxynucleotides (ODN) molecules, via biotin–streptavidin interaction. These peptide/oligonucleotide hybrid nanosystems are capable of bypassing prior limitations related with inactivated or live‐attenuated virus vaccines and achieve exceptionally high CD8+ T‐cell responses. The nanostructures are found to trigger strong IgG response and effectively modulate cross‐presentation of their antigen “cargo” through close proximity between the antigen and peptide/ODN adjuvant system. In addition, the biotinylated peptide nanofiber system is able to enhance antigen uptake and induce the maturation of antigen‐presenting cells. Due to its versatility, biocompatibility, and biodegradability with a broad variety of streptavidin‐linked antigens, the nanosystem shown here can be utilized as an efficient strategy for new vaccine development.Item Open Access Tenascin-C derived signaling induces neuronal differentiation in a three-dimensional peptide nanofiber gel(Royal Society of Chemistry, 2018) Sever, Melike; Gunay, Gokhan; Güler, Mustafa O.; Tekinay, Ayse B.The development of new biomaterials mimicking the neuronal extracellular matrix (ECM) requires signals for the induction of neuronal differentiation and regeneration. In addition to the biological and chemical cues, the physical properties of the ECM should also be considered while designing regenerative materials for nervous tissue. In this study, we investigated the influence of the microenvironment on tenascin-C signaling using 2D surfaces and 3D scaffolds generated by a peptide amphiphile nanofiber gel with a tenascin-C derived peptide epitope (VFDNFVLK). While tenascin-C mimetic PA nanofibers significantly increased the length and number of neurites produced by PC12 cells on 2D cell culture, more extensive neurite outgrowth was observed in the 3D gel environment. PC12 cells encapsulated within the 3D tenascin-C mimetic peptide nanofiber gel also exhibited significantly increased expression of neural markers compared to the cells on 2D surfaces. Our results emphasize the synergistic effects of the 3D conformation of peptide nanofibers along with the tenascin-C signaling and growth factors on the neuronal differentiation of PC12 cells, which may further provide more tissue-like morphology for therapeutic applications.Item Open Access Three-Dimensional Laminin Mimetic Peptide Nanofiber Gels for In Vitro Neural Differentiation(Wiley-VCH Verlag, 2017) Gunay, Gokhan; Sever, Melike; Tekinay, Ayse B.; Güler, Mustafa O.The extracellular matrix (ECM) provides biochemical signals and structural support for cells, and its functional imitation is a fundamental aspect of biomaterial design for regenerative medicine applications. The stimulation of neural differentiation by a laminin protein-derived epitope in two-dimensional (2D) and three-dimensional (3D) environments is investigated. The 3D gel system is found to be superior to its 2D counterpart for the induction of neural differentiation, even in the absence of a crucial biological inducer in nerve growth factor (NGF). In addition, cells cultured in 3D gels exhibits a spherical morphology that is consistent with their form under in vivo conditions. Overall, the present study underlines the impact of bioactivity, dimension, and NGF addition, as well as the cooperative effects thereof, on the neural differentiation of PC-12 cells. These results underline the significance of 3D culture systems in the development of scaffolds that closely replicate in vivo environments for the formation of cellular organoid models in vitro. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim