Browsing by Subject "Peptide amphiphile nanofibers"

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Open Access
Characterization of self-assembly and self-healing of peptide amphiphiles by atomic force microscopy
(2017-10) Dikeçoğlu, Fatma Begüm
Biological feedback mechanisms exert precise control over the initiation and termination of molecular self-assembly in response to environmental stimuli, while minimizing the formation and propagation of defects through self-repair processes. Peptide amphiphile (PA) molecules can self-assemble at physiological conditions to form supramolecular nanostructures that structurally and functionally resemble the nanofibrous proteins of the extracellular matrix (ECM), and their ability to reconfigure themselves in response to external stimuli is crucial for the design of intelligent systems. In this thesis, we investigated the real-time self-assembly, deformation, and self-healing of ECM-mimetic PA nanofibers in aqueous solution by using a force-stabilizing double-pass scanning AFM imaging method to disrupt the self-assembled peptide nanofibers in a force-dependent manner. We showed that nanofiber damage occurs at tip forces exceeding 1 nN, and that the damaged fibers subsequently recover under sub-nN tip forces. Fiber ends occasionally failed to reconnect following breakage and continue to grow as two individual nanofibers. Energy minimization calculations of nanofibers with increasing cross-sectional ellipticity (corresponding to varying levels of tip-induced fiber deformation) supported our observations, with high-ellipticity nanofibers exhibiting lower stability compared to their non-deformed counterparts. As a result, tip-mediated mechanical forces can provide an effective means of altering nanofiber integrity and visualizing the self-recovery of PA assemblies.
Open Access
Development and characterization of peptide nanofibers for cartilage regeneration
(2015-09) Yaylacı, Seher
Articular cartilage is a tissue that is continuously exposed to cyclical compressive stresses, but exhibits no capacity for self-healing following trauma. Cartilage has a dense extracellular matrix that is sparsely populated with cells, and the whole tissue lacks blood and lymphatic vessels, which complicates the cell infiltration response that ordinarily occurs during inflammation. In addition, the only cell type capable of synthesizing new cartilage matrix lies deeper in the tissue, near the bone boundary, and due to the dense extracellular matrix, chondrocytes cannot migrate to the defect site following injury. Consequently, cartilage tissue cannot effectively respond to treatment options. Treatment options exist for the short-term reduction of pain in smaller defects, but larger injuries necessitate tissue donation, and there is a severe shortage of articular cartilage that can be donated for autografting. Microfracture and autologous chondrocyte implantation are the current treatment options that use cellular therapy for the repair of cartilage. However, the cartilage tissue that forms in the course of these treatments is not the functional hyaline cartilage, but rather fibrous cartilage, which is mechanically weaker and degenerates over time. Tissue engineering studies using biodegradable scaffolds and autologous cells are gaining importance as effective long-term treatment options for the postinjury production of hyaline cartilage. Such scaffold systems are designed to be biodegradable and bioactive, which allows them to induce new tissue formation in shorter periods of time. In this dissertation, peptide nanofibers mimicking glycosaminoglycan molecules, which are important constituents of cartilage extracellular matrix, are designed and the effectiveness of these materials in terms of chondrocyte differentation are tested under in vitro conditions. As a follow-up study to in vitro experiments, the capacity of bioactive peptide nanofibers to support cartilage regeneration is evaluated in the rabbit osteochondral defect model. Structural and mechanical properties of newly deposited cartilage are highly dependent on the quality and quantity of its extracellular matrix, which also has a major impact on the integration of replacement cartilage into the surrounding healthy tissue. Signals provided by bioactive peptide nanofibers to cells at the defect site can strongly alter the quality of the newly synthesized extracellular matrix. Consequently, we designed glycosaminoglycanmimetic peptide nanofibers that closely imitate the structure of the native cartilage extracellular matrix and demonstrated that these nanofiber networks are able to induce the synthesis of collagen II and aggrecan molecules, which are the main constituents of cartilage tissue, during chondrogenic differentiation.
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.