Browsing by Author "Topal, A. E."

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Open Access
Atomic force microscopy for the investigation of molecular and cellular behavior
(Elsevier, 2016-10) Ozkan A.D.; Topal, A. E.; Dana, A.; Güler, Mustafa O.; Tekinay, A. B.
The present review details the methods used for the measurement of cells and their exudates using atomic force microscopy (AFM) and outlines the general conclusions drawn by the mechanical characterization of biological materials through this method. AFM is a material characterization technique that can be operated in liquid conditions, allowing its use for the investigation of the mechanical properties of biological materials in their native environments. AFM has been used for the mechanical investigation of proteins, nucleic acids, biofilms, secretions, membrane bilayers, tissues and bacterial or eukaryotic cells; however, comparison between studies is difficult due to variances between tip sizes and morphologies, sample fixation and immobilization strategies, conditions of measurement and the mechanical parameters used for the quantification of biomaterial response. Although standard protocols for the AFM investigation of biological materials are limited and minor differences in measurement conditions may create large discrepancies, the method is nonetheless highly effective for comparatively evaluating the mechanical integrity of biomaterials and can be used for the real-time acquisition of elasticity data following the introduction of a chemical or mechanical stimulus. While it is currently of limited diagnostic value, the technique is also useful for basic research in cancer biology and the characterization of disease progression and wound healing processes.
Open Access
Exploiting native Al2O3 for multispectral aluminum plasmonics
(American Chemical Society, 2014) Ayas S.; Topal, A. E.; Cupallari, A.; Güner, H.; Bakan, G.; Dana, A.
Aluminum, despite its abundance and low cost, is usually avoided for plasmonic applications due to losses in visible/infrared regimes and its interband absorption at 800 nm. Yet, it is compatible with silicon CMOS processes, making it a promising alternative for integrated plasmonic applications. It is also well known that a thin layer of native Al2O3 is formed on aluminum when exposed to air, which must be taken into account properly while designing plasmonic structures. Here, for the first time we report exploitation of the native Al2O3 layer for fabrication of periodic metal-insulator-metal (MIM) plasmonic structures that exhibit resonances spanning a wide spectral range, from the near-ultraviolet to mid-infrared region of the spectrum. Through fabrication of silver nanoislands on aluminum surfaces and MIM plasmonic surfaces with a thin native Al2O3 layer, hierarchical plasmonic structures are formed and used in surface-enhanced infrared spectroscopy (SEIRA) and surface-enhanced Raman spectrocopy (SERS) for detection of self-assembled monolayers of dodecanethiol. (Chemical Equation Presented). © 2014 American Chemical Society.
Open Access
Fabrication of supramolecular n/p-nanowires via coassembly of oppositely charged peptide-chromophore systems in aqueous media
(American Chemical Society, 2017-07) Khalily, M. A.; Bakan, G.; Kucukoz, B.; Topal, A. E.; Karatay, A.; Yaglioglu, H. G.; Dana, A.; Güler, Mustafa O.
Fabrication of supramolecular electroactive materials at the nanoscale with well-defined size, shape, composition, and organization in aqueous medium is a current challenge. Herein we report construction of supramolecular charge-transfer complex one-dimensional (1D) nanowires consisting of highly ordered mixed-stack π-electron donor-acceptor (D-A) domains. We synthesized n-type and p-type β-sheet forming short peptide-chromophore conjugates, which assemble separately into well-ordered nanofibers in aqueous media. These complementary p-type and n-type nanofibers coassemble via hydrogen bonding, charge-transfer complex, and electrostatic interactions to generate highly uniform supramolecular n/p-coassembled 1D nanowires. This molecular design ensures highly ordered arrangement of D-A stacks within n/p-coassembled supramolecular nanowires. The supramolecular n/p-coassembled nanowires were found to be formed by A-D-A unit cells having an association constant (KA) of 5.18 × 105 M-1. In addition, electrical measurements revealed that supramolecular n/p-coassembled nanowires are approximately 2400 and 10 times more conductive than individual n-type and p-type nanofibers, respectively. This facile strategy allows fabrication of well-defined supramolecular electroactive nanomaterials in aqueous media, which can find a variety of applications in optoelectronics, photovoltaics, organic chromophore arrays, and bioelectronics.
Open Access
Force and time-dependent self-assembly, disruption and recovery of supramolecular peptide amphiphile nanofibers
(Institute of Physics Publishing, 2018) Dikecoglu, F. B.; Topal, A. E.; Ozkan A.D.; Tekin, E. D.; Tekinay, A. B.; Güler, Mustafa O.; Dana, A.
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, and their ability to reconfigure themselves in response to external stimuli is crucial for the design of intelligent biomaterials systems. Here, we investigated real-time self-assembly, deformation, and recovery of PA nanofibers in aqueous solution by using a force-stabilizing double-pass scanning atomic force microscopy imaging method to disrupt the self-assembled peptide nanofibers in a force-dependent manner. We demonstrate that nanofiber damage occurs at tip-sample interaction forces exceeding 1 nN, and the damaged fibers subsequently recover when the tip pressure is reduced. Nanofiber ends occasionally fail 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) support our observations, with high-ellipticity nanofibers exhibiting lower stability compared to their non-deformed counterparts. Consequently, tip-mediated mechanical forces can provide an effective means of altering nanofiber integrity and visualizing the self-recovery of PA assemblies.
Open Access
Multivalent presentation of cationic peptides on supramolecular nanofibers for antimicrobial activity
(American Chemical Society, 2017) Beter, M.; Kara, H. K.; Topal, A. E.; Dana, A.; Tekinay, A. B.; Güler, Mustafa O.
Noncovalent and electrostatic interactions facilitate the formation of complex networks through molecular self-assembly in biomolecules such as proteins and glycosaminoglycans. Self-assembling peptide amphiphiles (PA) are a group of molecules that can form nanofibrous structures and may contain bioactive epitopes to interact specifically with target molecules. Here, we report the presentation of cationic peptide sequences on supramolecular nanofibers formed by self-assembling peptide amphiphiles for cooperative enhanced antibacterial activity. Antibacterial properties of self-assembled peptide nanofibers were significantly higher than soluble peptide molecules with identical amino acid sequences, suggesting that the tandem presentation of bioactive epitopes is important for designing new materials for bactericidal activity. In addition, bacteria were observed to accumulate more rapidly on peptide nanofibers compared to soluble peptides, which may further enhance antibacterial activity by increasing the number of peptide molecules interacting with the bacterial membrane. The cationic peptide amphiphile nanofibers were observed to attach to bacterial membranes and disrupt their integrity. These results demonstrate that short cationic peptides show a significant improvement in antibacterial activity when presented in the nanofiber form.
Open Access
Nanomechanical characterization of osteogenic differentiation of mesenchymal stem cells on bioactive peptide nanofiber hydrogels
(Wiley-VCH Verlag, 2017-08) Topal, A. E.; Tansik, G.; Ozkan A.D.; Güler, Mustafa O.; Dana, A.; Tekinay, A. B.
Stem cell differentiation is known to be influenced by the mechanical properties of the surrounding extracellular matrix (ECM); however, little is known about the mechanical phenotypes of differentiating stem cells within the ECM. Here, this study uses osteoinductive, ECM-mimetic peptide nanofibers to investigate the changes in the mechanical properties of rat mesenchymal stem cells (rMSCs) during osteogenic differentiation. In addition, octafluorocyclobutane (C4F8)-coated atomic force microscopy (AFM) cantilevers are developed to minimize tip–sample adhesion during the nanomechanical characterization of rMSCs, and osteogenic differentiation is monitored through molecular analysis in conjunction with AFM measurements. rMSCs cultured on osteoinductive peptide nanofibers differentiate at substantially higher rates, form osteogenic cell clusters, deposit calcium to the surrounding matrix, and strikingly increase their Young's moduli throughout the osteogenic differentiation process compared to controls. These results show that the elasticity profiles of differentiating rMSCs may change significantly depending on environmental factors and especially the degree of biomineralization, and that the natural elasticity responses of cells cultured on scaffolds may be considerably different from those observed on non-bioactive surfaces. This is important for the identification of cell elasticity as a biophysical marker of osteogenic differentiation of MSCs, and indicates that biomineralization might have a predominant role on cell mechanics.
Open Access
Newly designed silver coated-magnetic, monodisperse polymeric microbeads as SERS substrate for low-level detection of amoxicillin
(Elsevier, 2016-09) Kibar, G.; Topal, A. E.; Dana, A.; Tuncel, A.
We report the preparation of silver-coated magnetic polymethacrylate core-shell nanoparticles for use in surface-enhanced Raman scattering based drug detection. Monodisperse porous poly (mono-2-(methacryloyloxy)ethyl succinate-co-glycerol dimethacrylate), poly (MMES-co-GDMA) microbeads of ca. 5 μm diameter were first synthesized through a multistage microsuspension polymerization technique to serve as a carboxyl-bearing core region. Microspheres were subsequently magnetized by the co-precipitation of ferric ions, aminated through the surface hydroxyl groups and decorated with Au nanoparticles via electrostatic attraction. An Ag shell was then formed on top of the Au layer through a seed-mediated growth process, resulting in micron-sized monodisperse microbeads that exhibit Raman enhancement effects due to the roughness of the Ag surface layer. The core-shell microspheres were used as a new substrate for the detection of amoxicillin at trace concentrations up to 10-8 M by SERS. The proposed SERS platform can be evaluated as a useful tool for the follow-up amoxicillin pollution and low-level detection of amoxicillin in aqueous media.
Open Access
Probe microscopy methods and applications in imaging of biological materials
(Elsevier Ltd, 2018) Ozkan A.D.; Topal, A. E.; Dikecoglu, F. B.; Güler, Mustafa O.; Dana, A.; Tekinay, A. B.
Atomic force microscopy is an emerging tool for investigating the biomolecular aspects of cellular interactions; however, cell and tissue analyses must frequently be performed in aqueous environment, over rough surfaces, and on complex adhesive samples that complicate the imaging process and readily facilitate the blunting or fouling of the AFM probe. In addition, the shape and surface chemistry of the probe determine the quality and types of data that can be acquired from biological materials, with certain information becoming available only within a specific range of tip lengths or diameters, or through the assistance of specific chemical or biological functionalization procedures. Consequently, a broad range of probe modification techniques has been developed to extend the capabilities and overcome the limitations of biological AFM measurements, including the fabrication of AFM tips with specialized morphologies, surface coating with biologically affine molecules, and the attachment of proteins, nucleic acids and cells to AFM probes. In this review, we underline the importance of probe choice and modification for the AFM analysis of biomaterials, discuss the recent literature on the use of non-standard AFM tips in life sciences research, and consider the future utility of tip functionalization methods for the investigation of fundamental cell and tissue interactions. © 2017 Elsevier Ltd
Open Access
Sensitivity comparison of localized plasmon resonance structures and prism coupler
(2014) Kaya, Y.; Ayas S.; Topal, A. E.; Guner, H.; Dana, A.
Plasmon resonances are widely used in biomolecular sensing and continue to be an active research field due to the rich variety of surface and measurement configurations, some of which exhibit down to single molecule level sensitivity. The resonance wavelength shift of the plasmonic structure upon binding of molecules, strongly depends, among other parameters, on how well the field of the resonant mode is confined to the binding site. Here it is shown that, by using properly designed metal-insulator-metal type resonators, improved wavelength response can be achieved with localized surface plasmon resonators (LSPRs) compared to that of the commonly used Kretschmann geometry. Using computational tools we investigate theoretically the refractive index response of several LSPR structures to a 2 nm thin film of binding molecules. LSPR resonators are shown to feature improved sensitivity over conventional Kretschmann geometry in the wavelength interrogation scheme for such a thin film. Moreover, some of the LSPR modes are quasi-omnidirectional and such angular independence (up to 30 angle of incidence) allows higher numerical apertures to be used in colorimetric imaging. Results highlight the potential of LSPRs for biomolecular sensing with high sensitivity and high spatial resolution.
Open Access
A smartphone based surface plasmon resonance imaging (SPRi) platform for on-site biodetection
(Elsevier, 2017) Guner, H.; Ozgur, E.; Kokturk, G.; Celik, M.; Esen, E.; Topal, A. E.; Ayas, S.; Uludag, Y.; Elbuken, C.; Dana, A.
We demonstrate a surface plasmon resonance imaging platform integrated with a smartphone to be used in the field with high-throughput biodetection. Inexpensive and disposable SPR substrates are produced by metal coating of commercial Blu-ray discs. A compact imaging apparatus is fabricated using a 3D printer which allows taking SPR measurements from more than 20.000 individual pixels. Real-time bulk refractive index change measurements yield noise equivalent refractive index changes as low as 4.12 × 10−5 RIU which is comparable with the detection performance of commercial instruments. As a demonstration of a biological assay, we have shown capture of mouse IgG antibodies by immobilized layer of rabbit anti-mouse (RAM) IgG antibody with nanomolar level limit of detection. Our approach in miniaturization of SPR biosensing in a cost-effective manner could enable realization of portable SPR measurement systems and kits for point-of-care applications.
Open Access
Virus-like nanostructures for tuning immune response
(Nature Publishing Group, 2015) Mammadov R.; Cinar, G.; Gunduz, N.; Goktas, M.; Kayhan, H.; Tohumeken, S.; Topal, A. E.; Orujalipoor, I.; Delibasi, T.; Dana, A.; Ide, S.; Tekinay, A. B.; Güler, Mustafa O.
Synthetic vaccines utilize viral signatures to trigger immune responses. Although the immune responses raised against the biochemical signatures of viruses are well characterized, the mechanism of how they affect immune response in the context of physical signatures is not well studied. In this work, we investigated the ability of zero-and one-dimensional self-assembled peptide nanostructures carrying unmethylated CpG motifs (signature of viral DNA) for tuning immune response. These nanostructures represent the two most common viral shapes, spheres and rods. The nanofibrous structures were found to direct immune response towards Th1 phenotype, which is responsible for acting against intracellular pathogens such as viruses, to a greater extent than nanospheres and CpG ODN alone. In addition, nanofibers exhibited enhanced uptake into dendritic cells compared to nanospheres or the ODN itself. The chemical stability of the ODN against nucleasemediated degradation was also observed to be enhanced when complexed with the peptide nanostructures. In vivo studies showed that nanofibers promoted antigen-specific IgG production over 10-fold better than CpG ODN alone. To the best of our knowledge, this is the first report showing the modulation of the nature of an immune response through the shape of the carrier system.