Browsing by Author "Tekinay, Ayse B."

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Open Access
Alkaline phosphatase-mimicking peptide nanofibers for osteogenic differentiation
(American Chemical Society, 2015) Gülseren, Gülcihan; Yasa, I. Ceren; Ustahuseyin, Oya; Tekin, E. Deniz; Tekinay, Ayse B.; Güler, Mustafa O.
Recognition of molecules and regulation of extracellular matrix synthesis are some of the functions of enzymes in addition to their catalytic activity. While a diverse array of enzyme-like materials have been developed, these efforts have largely been confined to the imitation of the chemical structure and catalytic activity of the enzymes, and it is unclear whether enzyme-mimetic molecules can also be used to replicate the matrix-regulatory roles ordinarily performed by natural enzymes. Self-assembled peptide nanofibers can provide multifunctional enzyme-mimetic properties, as the active sequences of the target enzymes can be directly incorporated into the peptides. Here, we report enhanced bone regeneration efficiency through peptide nanofibers carrying both catalytic and matrix-regulatory functions of alkaline phosphatase, a versatile enzyme that plays a critical role in bone formation by regulating phosphate homeostasis and calcifiable bone matrix formation. Histidine presenting peptide nanostructures were developed to function as phosphatases. These molecules are able to catalyze phosphate hydrolysis and serve as bone-like nodule inducing scaffolds. Alkaline phosphatase-like peptide nanofibers enabled osteogenesis for both osteoblast-like and mesenchymal cell lines.
Open Access
Amyloid inspired self-assembled peptide nanofibers
(American Chemical Society, 2012) Çınar, Göksu; Ceylan, Hakan; Urel, Mustafa; Erkal, Turan S.; Tekin, E. Deniz; Tekinay, Ayse B.; Dâna, Aykutlu; Güler, Mustafa O.
Amyloid peptides are important components in many degenerative diseases as well as in maintaining cellular metabolism. Their unique stable structure provides new insights in developing new materials. Designing bioinspired self-assembling peptides is essential to generate new forms of hierarchical nanostructures. Here we present oppositely charged amyloid inspired peptides (AIPs), which rapidly self-assemble into nanofibers at pH 7 upon mixing in water caused by noncovalent interactions. Mechanical properties of the gels formed by self-assembled AIP nanofibers were analyzed with oscillatory rheology. AIP gels exhibited strong mechanical characteristics superior to gels formed by self-assembly of previously reported synthetic short peptides. Rheological studies of gels composed of oppositely charged mixed AIP molecules (AIP-1 + 2) revealed superior mechanical stability compared to individual peptide networks (AIP-1 and AIP-2) formed by neutralization of net charges through pH change. Adhesion and elasticity properties of AIP mixed nanofibers and charge neutralized AIP-1, AIP-2 nanofibers were analyzed by high resolution force-distance mapping using atomic force microscopy (AFM). Nanomechanical characterization of self-assembled AIP-1 + 2, AIP-1, and AIP-2 nanofibers also confirmed macroscopic rheology results, and mechanical stability of AIP mixed nanofibers was higher compared to individual AIP-1 and AIP-2 nanofibers self-assembled at acidic and basic pH, respectively. Experimental results were supported with molecular dynamics simulations by considering potential noncovalent interactions between the amino acid residues and possible aggregate forms. In addition, HUVEC cells were cultured on AIP mixed nanofibers at pH 7 and biocompatibility and collagen mimetic scaffold properties of the nanofibrous system were observed. Encapsulation of a zwitterionic dye (rhodamine B) within AIP nanofiber network was accomplished at physiological conditions to demonstrate that this network can be utilized for inclusion of soluble factors as a scaffold for cell culture studies. © 2012 American Chemical Society.
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.
Open Access
Bioactive nanomaterials for neural engineering
(Springer, Cham, 2016) Sever, Melike; Uyan, İdil; Tekinay, Ayse B.; Güler, Mustafa O.; Zhang, L. G.; Kaplan, D. L.
Nervous system is a highly complex interconnected network and higher organisms including humans have limited neural regeneration capacity. Neurodegenerative diseases result in significant cognitive, sensory, or motor impairments. Following an injury in the neural network, there is a balance between promotion and inhibition of regeneration and this balance is shifted to different directions in central nervous system (CNS) and peripheral nervous system (PNS). More regeneration capacity is observed in the PNS compared to the CNS. Although, several mechanisms play roles in the inhibitory and growth-promoting natures of the CNS and PNS, extracellular matrix (ECM) elements are key players in this process. ECM is a three-dimensional environment where the cells migrate, proliferate, and differentiate (Rutka et al. 1988; Pan et al. 1997). After a comprehensive investigation of the interactions between the ECM proteins and cell receptors, the ECM environment was found to regulate significant cellular processes such as survival, proliferation, differentiation, and migration (Yurchenco and Cheng 1994; Aszodi et al. 2006). Its components have major roles not only in neurogenesis during development of the nervous system but also in normal neural functioning during adulthood (Hubert et al. 2009).
Open Access
Biocompatible electroactive tetra (aniline)-conjugated peptide nanofibers for neural differentiation
(American Chemical Society, 2018) Arioz, Idil; Erol, Ozlem; Bakan, Gokhan; Dikecoglu, F. Begum; Topal, Ahmet E.; Urel, Mustafa; Dana, Aykutlu; Tekinay, Ayse B.; Güler, Mustafa O.
Peripheral nerve injuries cause devastating problems for the quality of patients' lives, and regeneration following damage to the peripheral nervous system is limited depending on the degree of the damage. Use of nanobiomaterials can provide therapeutic approaches for the treatment of peripheral nerve injuries. Electroactive biomaterials, in particular, can provide a promising cure for the regeneration of nerve defects. Here, a supramolecular electroactive nanosystem with tetra(aniline) (TA)-containing peptide nanofibers was developed and utilized for nerve regeneration. Self-assembled TA-conjugated peptide nanofibers demonstrated electroactive behavior. The electroactive self-assembled peptide nanofibers formed a well-defined three-dimensional nanofiber network mimicking the extracellular matrix of the neuronal cells. Neurite outgrowth was improved on the electroactive TA nanofiber gels. The neural differentiation of PC-12 cells was more advanced on electroactive peptide nanofiber gels, and these biomaterials are promising for further use in therapeutic neural regeneration applications.
Open Access
Biosensors for early disease diagnosis
(John Wiley & Sons, 2016-03-11) Topal, Ahmet E.; Özkan, Alper Devrim; Dana, Aykutlu; Tekinay, Ayse B.; Güler, Mustafa O.; Güler, Mustafa O.; Tekinay, Ayşe B.
This chapter focuses on biosensor types, their detection limits, analysis times, and the diseases they are suitable for detecting. In addition, as nanomaterials are an effective means of producing small‐scale diagnostic devices, nanostructures have been commonly employed in biosensor design. Consequently, a section is devoted to the types of nanomaterials currently under use in biosensor design. Biosensors can be classified according to their recognition element (e.g., enzymes, antibodies, nucleic acids), output type (e.g., optical, electrical, mechanical), detection principle (e.g., surface plasmon resonance (SPR) based, surface‐enhanced Raman spectroscopy (SERS) based, quartz crystal microbalance (QCM) based), or intended use (in vivo or ex vivo). These factors all play vital roles in determining the sensitivity and selectivity of a biosensor and are considered separately.
Open Access
Bone-like mineral nucleating peptide nanofibers induce differentiation of human mesenchymal stem cells into mature osteoblasts
(American Chemical Society, 2014) Ceylan, Hakan; Kocabey, Samet; Gulsuner, Hilal Unal; Balcik, O. S.; Güler, Mustafa O.; Tekinay, Ayse B.
A bone implant should integrate to the tissue through a bone-like mineralized interface, which requires increased osteoblast activity at the implant-tissue boundary. Modification of the implant surface with synthetic bioinstructive cues facilitates on-site differentiation of progenitor stem cells to functional mature osteoblasts and results in subsequent mineralization. Inspired by the bioactive domains of the bone extracellular matrix proteins and the mussel adhesive proteins, we synthesized peptide nanofibers to promote bone-like mineralization on the implant surface. Nanofibers functionalized with osteoinductive collagen I derived Asp-Gly-Glu-Ala (DGEA) peptide sequence provide an advantage in initial adhesion, spreading, and early commitment to osteogenic differentiation for mesenchymal stem cells (hMSCs). In this study, we demonstrated that this early osteogenic commitment, however, does not necessarily guarantee a priority for maturation into functional osteoblasts. Similar to natural biological cascades, early commitment should be further supported with additional signals to provide a long-term effect on differentiation. Here, we showed that peptide nanofibers functionalized with Glu-Glu-Glu (EEE) sequence enhanced mineralization abilities due to osteoinductive properties for late-stage differentiation of hMSCs. Mussel-inspired functionalization not only enables robust immobilization on metal surfaces, but also improves bone-like mineralization under physiologically simulated conditions. The multifunctional osteoinductive peptide nanofiber biointerfaces presented here facilitate osseointegration for long-term clinical stability. © 2014 American Chemical Society.
Open Access
Cell penetrating peptide amphiphile integrated liposomal systems for enhanced delivery of anticancer drugs to tumor cells
(Royal Society of Chemistry, 2013) Sardan, Melis; Kilinc, Murat; Genç, Rukan; Tekinay, Ayse B.; Güler, Mustafa O.
Liposomes have been extensively used as effective nanocarriers, providing better solubility, higher stability and slower release of drugs compared to free drug administration. They are also preferred due to their nontoxic nature as well as their biodegradability and cell membrane mimicking abilities. In this study, we examined noncovalent integration of a cell penetrating arginine-rich peptide amphiphile into a liposomal formulation of negatively charged 1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DOPG) phospholipids in the presence of cholesterol due to its amphipathic character. We studied changes in the physical characteristics (size, surface potential and membrane polarity) of the liposomal membrane, as well as in the encapsulation of hydrophilic and hydrophobic agents due to peptide amphiphile incorporation. The activities of peptide integrated liposomal systems as drug delivery agents were investigated by using anti-cancer drugs, doxorubicin-HCl and paclitaxel. Enhancement in liposomal uptake due to arginine-rich peptide integration, and enhanced efficacy of the drugs were observed with peptide functionalized liposomes compared to free drugs. © 2013 The Royal Society of Chemistry.
Open Access
Cooperative effect of heparan sulfate and laminin mimetic peptide nanofibers on the promotion of neurite outgrowth
(Elsevier, 2012) Mammadov, Busra; Mammadov, Rashad; Güler, Mustafa O.; Tekinay, Ayse B.
Extracellular matrix contains an abundant variety of signals that are received by cell surface receptors contributing to cell fate, via regulation of cellular activities such as proliferation, migration and differentiation. Cues from extracellular matrix can be used for the development of materials to direct cells into their desired fate. Neural extracellular matrix (ECM) is rich in axonal growth inducer proteins, and by mimicking these permissive elements in the cellular environment, neural differentiation as well as neurite outgrowth can be induced. In this paper, we used a synthetic peptide nanofiber system that can mimic not only the activity of laminin, an axonal growth-promoting constituent of the neural ECM, but also the activity of heparan sulfate proteoglycans in order to induce neuritogenesis. Heparan sulfate mimetic groups that were utilized in our system have an affinity to growth factors and induce the neuroregenerative effect of laminin mimetic peptide nanofibers. The self-assembled peptide nanofibers with heparan sulfate mimetic and laminin-derived epitopes significantly promoted neurite outgrowth by PC-12 cells. In addition, these scaffolds were even effective in the presence of chondroitin sulfate proteoglycans (CSPGs), which are the major inhibitory components of the central nervous system. In the presence of these nanofibers, cells could overcome CSPG inhibitory effect and extend neurites on peptide nanofiber scaffolds. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Open Access
Dentin phosphoprotein mimetic peptide nanofibers promote biomineralization
(WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim, 2019) Gülseren, Gülcihan; Tansik, Gülistan; Garifullin, Ruslan; Tekinay, Ayse B.; Güler, Mustafa O.
Dentin phosphoprotein (DPP) is a major component of the dentin matrix playing crucial role in hydroxyapatite deposition during bone mineralization, making it a prime candidate for the design of novel materials for bone and tooth regeneration. The bioactivity of DPP‐derived proteins is controlled by the phosphorylation and dephosphorylation of the serine residues. Here an enzyme‐responsive peptide nanofiber system inducing biomineralization is demonstrated. It closely emulates the structural and functional properties of DPP and facilitates apatite‐like mineral deposition. The DPP‐mimetic peptide molecules self‐assemble through dephosphorylation by alkaline phosphatase (ALP), an enzyme participating in tooth and bone matrix mineralization. Nanofiber network formation is also induced through addition of calcium ions. The gelation process following nanofiber formation produces a mineralized extracellular matrix like material, where scaffold properties and phosphate groups promote mineralization. It is demonstrated that the DPP‐mimetic peptide nanofiber networks can be used for apatite‐like mineral deposition for bone regeneration.
Open Access
Design of a Gd-DOTA-phthalocyanine conjugate combining MRI contrast imaging and photosensitization properties as a potential molecular theranostic
(Wiley-Blackwell Publishing, Inc., 2014) Tekdaş, D. A.; Garifullin, Ruslan; Şentürk, Berna; Zorlu, Y.; Gundogdu, Umut; Atalar, Ergin; Tekinay, Ayse B.; Chernonosov, A. A.; Yerli, Y.; Dumoulin, F.; Güler, Mustafa O.; Ahsen, V.; Gürek, A. G.
The design and synthesis of a phthalocyanine - Gd-DOTA conjugate is presented to open the way to novel molecular theranostics, combining the properties of MRI contrast imaging with photodynamic therapy. The rational design of the conjugate integrates isomeric purity of the phthalocyanine core substitution, suitable biocompatibility with the use of polyoxo water-solubilizing substituents, and a convergent synthetic strategy ended by the use of click chemistry to graft the Gd-DOTA moiety to the phthalocyanine. Photophysical and photochemical properties, contrast imaging experiments and preliminary in vitro investigations proved that such a combination is relevant and lead to a new type of potential theranostic agent.
Open Access
Diabetic wound regeneration using heparin-mimetic peptide amphiphile gel in db/db mice
(Royal Society of Chemistry, 2017) Senturk, Berna; Demircan, Burak M.; Ozkan, Alper D.; Tohumeken, Sehmus; Delibasi, T.; Güler, Mustafa O.; Tekinay, Ayse B.
There is an urgent need for more efficient treatment of chronic wounds in diabetic patients especially with a high risk of leg amputation. Biomaterials capable of presenting extracellular matrix-mimetic signals may assist in the recovery of diabetic wounds by creating a more conducive environment for blood vessel formation and modulating the immune system. In a previous study, we showed that glycosaminoglycan-mimetic peptide nanofibers are able to increase the rate of closure in STZ-induced diabetic rats by induction of angiogenesis. The present study investigates the effect of a heparin-mimetic peptide amphiphile (PA) nanofiber gel on full-thickness excisional wounds in a db/db diabetic mouse model, with emphasis on the ability of the PA nanofiber network to regulate angiogenesis and the expression of pro-inflammatory cytokines. Here, we showed that the heparin-mimetic PA gel can support tissue neovascularization, enhance the deposition of collagen and expression of alpha-smooth muscle actin (α-SMA), and eliminate the sustained presence of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the diabetic wound site. As the absence of neovascularization and overexpression of pro-inflammatory markers are a hallmark of diabetes and interfere with wound recovery by preventing the healing process, the heparin-mimetic PA treatment is a promising candidate for acceleration of diabetic wound healing by modulating angiogenesis and local immune response. © 2017 The Royal Society of Chemistry.
Open Access
Glycosaminoglycan mimetric peptide nanofibers promote mineralization by osteogenic cells
(Elsevier, 2013) Kocabey, Samet; Ceylan, Hakan; Tekinay, Ayse B.; Güler, Mustafa O.
Bone tissue regeneration is accomplished by concerted regulation of protein-based extracellular matrix components, glycosaminoglycans (GAGs) and inductive growth factors. GAGs constitute a significant portion of the extracellular matrix and have a significant impact on regulating cellular behavior, either directly or through encapsulation and presentation of growth factors to the cells. In this study we utilized a supramolecular peptide nanofiber system that can emulate both the nanofibrous architecture of collagenous extracellular matrix and the major chemical composition found on GAGs. GAGs and collagen mimetic peptide nanofibers were designed and synthesized with sulfonate and carboxylate groups on the peptide scaffold. The GAG mimetic peptide nanofibers interact with bone morphogenetic protein-2 (BMP-2), which is a critical growth factor for osteogenic activity. The GAG mimicking ability of the peptide nanofibers and their interaction with BMP-2 promoted osteogenic activity and mineralization by osteoblastic cells. Alkaline phosphatase activity, Alizarin red staining and energy dispersive X-ray analysis spectroscopy indicated the efficacy of the peptide nanofibers in inducing mineralization. The multifunctional and bioactive microenvironment presented here provides osteoblastic cells with osteogenic stimuli similar to those observed in native bone tissue.
Open Access
Heparin mimetic peptide nanofibers promote angiogenesis
(Biomacromolecules, 2011) Mammadov, Rashad; Mammadov, Busra; Toksoz, Sıla; Aydin, B.; Yagci, R.; Tekinay, Ayse B.; Güler, Mustafa O.
New blood vessel formation (angiogenesis) is one of the most important processes required for functional tissue formation. Induction of angiogenesis is usually triggered by growth factors released by cells. Glycosaminoglycans (e.g., heparan sulphates) in the extracellular matrix aid in proper functioning of these growth factors. Therefore, exogeneous heparin or growth factors were required for promoting angiogenesis in previous regenerative medicine studies. Here we report for the first time induction of angiogenesis by a synthetic nanofibrous peptide scaffold without the addition of any exogenous growth factors or heparin. We designed and synthesized a self-assembling peptide amphiphile molecule that is functionalized with biologically active groups to mimic heparin. Like heparin, this molecule has the ability to interact with growth factors and effectively enhance their bioactivity. The nanofibers formed by these molecules were shown to form a 3D network mimicking the structural proteins in the extracellular matrix. Because of heparin mimicking capabilities of the peptide nanofibers, angiogenesis was induced without the addition of exogenous growth factors in vitro. Bioactive interactions between the nanofibers and the growth factors enabled robust vascularization in vivo as well. Heparin mimetic peptide nanofibers presented here provide new opportunities for angiogenesis and tissue regeneration by avoiding the use of heparin and exogenous growth factors. The synthetic peptide nanofiber scaffolds enriched with proper chemical functional groups shown in this study can be used to induce various desired physiological responses for tissue regeneration. © 2011 American Chemical Society.
Open Access
Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels
(Elsevier, 2015) Uzunalli, Gözde; Tumtas, Yasin; Delibasi, T.; Yasa, Oncay; Mercan, S.; Güler, Mustafa O.; Tekinay, Ayse B.
Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a proper mechanically and biologically supportive environment for enhancing both in vitro islet culture and transplantation efficiency. Here, we demonstrate that heparin mimetic peptide amphiphile (HM-PA) nanofibrous network is a promising platform for these purposes. The islets cultured with peptide nanofiber gel containing growth factors exhibited a similar glucose stimulation index as that of the freshly isolated islets even after 7 days. After transplantation of islets to STZ-induced diabetic rats, 28 day-long monitoring displayed that islets that were transplanted in HM-PA nanofiber gels maintained better blood glucose levels at normal levels compared to the only islet transplantation group. In addition, intraperitoneal glucose tolerance test revealed that animals that were transplanted with islets within peptide gels showed a similar pattern with the healthy control group. Histological assessment showed that islets transplanted within peptide nanofiber gels demonstrated better islet integrity due to increased blood vessel density. This work demonstrates that using the HM-PA nanofiber gel platform enhances the islets function and islet transplantation efficiency both in vitro and in vivo.
Open Access
Intracellular accumulation of gold nanoparticles leads to inhibition of macropinocytosis to reduce the endoplasmic reticulum stress
(Nature Publishing Group, 2017) Gunduz, Nuray; Ceylan, H.; Güler, Mustafa O.; Tekinay, Ayse B.
Understanding the toxicity of nanomaterials remains largely limited to acute cellular response, i.e., short-Term in vitro cell-death based assays, and analyses of tissue-and organ-level accumulation and clearance patterns in animal models, which have produced very little information about how these materials (from the toxicity point of view) interact with the complex intracellular machinery. In particular, understanding the mechanism of toxicity caused by the gradual accumulation of nanomaterials due to prolonged exposure times is essential yet still continue to be a largely unexplored territory. Herein, we show intracellular accumulation and the associated toxicity of gold nanoparticles (AuNPs) for over two-months in the cultured vascular endothelial cells. We observed that steady exposure of AuNPs at low (non-lethal) dose leads to rapid intracellular accumulation without causing any detectable cell death while resulting in elevated endoplasmic reticulum (ER) stress. Above a certain intracellular AuNP threshold, inhibition of macropinocytosis mechanism ceases further nanoparticle uptake. Interestingly, the intracellular depletion of nanoparticles is irreversible. Once reaching the maximum achievable intracellular dose, a steady depletion is observed, while no cell death is observed at any stage of this overall process. This depletion is important for reducing the ER stress. To our knowledge, this is the first report suggesting active regulation of nanoparticle uptake by cells and the impact of long-Term exposure to nanoparticles in vitro. © 2017The Author(s).
Open Access
Microscopic characterization of peptide nanostructures
(Elsevier, 2012) Mammadov, Rashad; Tekinay, Ayse B.; Dana, Aykutlu; Güler, Mustafa O.
Peptide-based nanomaterials have been utilized for various applications from regenerative medicine to electronics since they provide several advantages including easy synthesis methods, numerous routes for functionalization and biomimicry of secondary structures of proteins which leads to design of self-assembling peptide molecules to form nanostructures. Microscopic characterization at nanoscale is critical to understand processes directing peptide molecules to self-assemble and identify structure-function relationship of the nanostructures. Here, fundamental studies in microscopic characterization of peptide nanostructures are discussed to provide insights in widely used microscopy tools. In this review, we will encompass characterization studies of peptide nanostructures with modern microscopes, such as TEM, SEM, AFM, and advanced optical microscopy techniques. We will also mention specimen preparation methods and describe interpretation of the images. © 2011 Elsevier Ltd.
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.
Open Access
Multi-domain short peptide molecules for in situ synthesis and biofunctionalization of gold nanoparticles for integrin-targeted cell uptake
(American Chemical Society, 2015) Gülsuner, Hilal Ünal; Ceylan, Hakan; Güler, Mustafa O.; Tekinay, Ayse B.
We describe design and synthesis model of multidomain (modular) peptides (MDPs), which direct a reaction cascade coupling the synthesis and surface functionalization of gold nanoparticles (AuNPs) in a single step. The synthesis is achieved via simple mixing of the aqueous solutions of auric acid and MDPs at room temperature without the addition of any surfactants or toxic intermediate reagents. This method allows facile control over the nanoparticle size between ∼2–15 nm, which opens a practical window for biomedical applications. In contrast to the conventional citrate-mediated methods, peptide-mediated synthesis and stabilization provide increased colloidal stability to AuNPs. As a proof of this concept, we demonstrate active targeting of human breast adenocarcinoma cell line (MCF7) using the one-step-prepared engineered AuNPs. Overall, we propose a single-step, chemically greener, biologically safer method for the synthesis and surface functionalization of gold nanoparticles in a size-controlled manner. The chemical versatility of the MDP design broadens the applicability of this strategy, thereby emerging as a successful alternative for the currently available nanoparticle preparation technologies.
Open Access
Mussel inspired dynamic cross-linking of self-healing peptide nanofiber network
(Wiley, 2013) Ceylan, Hakan; Urel, Mustafa; Erkal, Turan S.; Tekinay, Ayse B.; Dana, Aykutlu; Güler, Mustafa O.
A general drawback of supramolecular peptide networks is their weak mechanical properties. In order to overcome a similar challenge, mussels have adapted to a pH-dependent iron complexation strategy for adhesion and curing. This strategy also provides successful stiffening and self-healing properties. The present study is inspired by the mussel curing strategy to establish iron cross-link points in self-assembled peptide networks. The impact of peptide-iron complexation on the morphology and secondary structure of the supramolecular nanofibers is characterized by scanning electron microscopy, circular dichroism and Fourier transform infrared spectroscopy. Mechanical properties of the cross-linked network are probed by small angle oscillatory rheology and nanoindentation by atomic force microscopy. It is shown that iron complexation has no influence on self-assembly and β-sheet-driven elongation of the nanofibers. On the other hand, the organic-inorganic hybrid network of iron cross-linked nanofibers demonstrates strong mechanical properties comparable to that of covalently cross-linked network. Strikingly, iron cross-linking does not inhibit intrinsic reversibility of supramolecular peptide polymers into disassembled building blocks and the self-healing ability upon high shear load. The strategy described here could be extended to improve mechanical properties of a wide range of supramolecular polymer networks. A simple and versatile method for improving mechanical performance of supramolecular polymers is described. Inspired by a mussel curing mechanism, reversible iron cross-linking into a self-assembled peptide network significantly enhances the mechanical properties while having no impact on the β-sheet-driven self-assembly. The network retains its pH-dependent reversibility and self-healing properties. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.