Browsing by Subject "Cells"
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Item Open Access Analysis of blood cell production under growth factors switching(Elsevier B.V., 2017) Djema, W.; Özbay, Hitay; Bonnet, C.; Fridman, E.; Mazenc, F.; Clairambault, J.Hematopoiesis is a highly complicated biological phenomenon. Improving its mathematical modeling and analysis are essential steps towards consolidating the common knowledge about mechanisms behind blood cells production. On the other hand, trying to deepen the mathematical modeling of this process has a cost and may be highly demanding in terms of mathematical analysis. In this paper, we propose to describe hematopoiesis under growth factor-dependent parameters as a switching system. Thus, we consider that different biological functions involved in hematopoiesis, including aging velocities, are controlled through multiple growth factors. Then we attempt a new approach in the framework of time-delay switching systems, in order to interpret the behavior of the system around its possible positive steady states. We start here with the study of a specific case in which switching is assumed to result from drug infusions. In a broader context, we expect that interpreting cell dynamics using switching systems leads to a good compromise between complexity of realistic models and their mathematical analysis. © 2017Item Open Access Analysis of mutual acoustic coupling in CMUT arrays using an accurate lumped element nonlinear equivalent circuit model(2012) Oğuz, H.Kağan; Atalar, Abdullah; Köymen, HayrettinWe use an accurate nonlinear equivalent circuit model to analyze CMUT arrays with multiple cells, where every cell in the array is coupled to other cells at their acoustic terminals through a mutual radiation impedance matrix. We get results comparable to finite element analysis accuracy. Hence, the analysis of a large array becomes a circuit theory problem and can be scrutinized with circuit simulators. We study the mutual acoustic interactions that arise through the immersion medium due to the influence of the generated pressure field by each cell on the others. We compare the performance of different 1D cMUT arrays, where each element is half-wavelength wide and 10 and 20 wavelengths long at the resonance frequency of a single cell. © 2012 IEEE.Item Open Access Analysis of the in vitro nanoparticle–cell interactions via a smoothing-splines mixed-effects model(Taylor and Francis, 2016) Dogruoz, E.; Dayanik, S.; Budak, G.; Sabuncuoglu, I.A mixed-effects statistical model has been developed to understand the nanoparticle (NP)–cell interactions and predict the rate of cellular uptake of NPs. NP–cell interactions are crucial for targeted drug delivery systems, cell-level diagnosis, and cancer treatment. The cellular uptake of NPs depends on the size, charge, chemical structure, and concentration of NPs, and the incubation time. The vast number of combinations of these variable values disallows a comprehensive experimental study of NP–cell interactions. A mathematical model can, however, generalize the findings from a limited number of carefully designed experiments and can be used for the simulation of NP uptake rates, to design, plan, and compare alternative treatment options. We propose a mathematical model based on the data obtained from in vitro interactions of NP–healthy cells, through experiments conducted at the Nanomedicine and Advanced Technologies Research Center in Turkey. The proposed model predicts the cellular uptake rate of silica, polymethyl methacrylate, and polylactic acid NPs, given the incubation time, size, charge and concentration of NPs. This study implements the mixed-model methodology in the field of nanomedicine for the first time, and is the first mathematical model that predicts the rate of cellular uptake of NPs based on sound statistical principles. Our model provides a cost-effective tool for researchers developing targeted drug delivery systems.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 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.Item Open Access Bacteria encapsulated electrospun nanofibrous webs for remediation of methylene blue dye in water(Elsevier, 2017-04) Sarioglu O.F.; Keskin, N. O. S.; Celebioglu A.; Tekinay, T.; Uyar, TamerIn this study, preparation and application of novel biocomposite materials that were produced by encapsulation of bacterial cells within electrospun nanofibrous webs are described. A commercial strain of Pseudomonas aeruginosa which has methylene blue (MB) dye remediation capability was selected for encapsulation, and polyvinyl alcohol (PVA) and polyethylene oxide (PEO) were selected as the polymer matrices for the electrospinning of bacteria encapsulated nanofibrous webs. Encapsulation of bacterial cells was monitored by scanning electron microscopy (SEM) and fluorescence microscopy, and the viability of encapsulated bacteria was checked by live/dead staining and viable cell counting assay. Both bacteria/PVA and bacteria/PEO webs have shown a great potential for remediation of MB, yet bacteria/PEO web has shown higher removal performances than bacteria/PVA web, which was probably due to the differences in the initial viable bacterial cells for those two samples. The bacteria encapsulated electrospun nanofibrous webs were stored at 4 °C for three months and they were found as potentially storable for keeping encapsulated bacterial cells alive. Overall, the results suggest that electrospun nanofibrous webs are suitable platforms for preservation of living bacterial cells and they can be used directly as a starting inoculum for bioremediation of water systems.Item Open Access Bioactive supramolecular peptide nanofibers for regenerative medicine(Wiley, 2014) Arslan, Elif; Garip, I. Ceren; Gulseren, Gulcihan; Tekinay, Ayse B.; Güler, Mustafa O.Recent advances in understanding of cell-matrix interactions and the role of the extracellular matrix (ECM) in regulation of cellular behavior have created new perspectives for regenerative medicine. Supramolecular peptide nanofiber systems have been used as synthetic scaffolds in regenerative medicine applications due to their tailorable properties and ability to mimic ECM proteins. Through designed bioactive epitopes, peptide nanofiber systems provide biomolecular recognition sites that can trigger specific interactions with cell surface receptors. The present Review covers structural and biochemical properties of the self-assembled peptide nanofibers for tissue regeneration, and highlights studies that investigate the ability of ECM mimetic peptides to alter cellular behavior including cell adhesion, proliferation, and/or differentiation.Item Open Access Carcinoma cell line discrimination in microscopic images using unbalanced wavelets(IEEE, 2012-03) Keskin, Furkan; Suhre, Alexander; Erşahin, Tüli,; Çetin Atalay, Rengül; Çetin, A. EnisCancer cell lines are widely used for research purposes in laboratories all over the world. In this paper, we present a novel method for cancer cell line image classification, which is very costly by conventional methods. The aim is to automatically classify 14 different classes of cell lines including 7 classes of breast and 7 classes of liver cancer cells. Microscopic images containing irregular carcinoma cell patterns are represented by randomly selected subwindows which possibly correspond to foreground pixels. For each subwindow, a correlation descriptor utilizing the fractional unbalanced wavelet transform coefficients and several morphological attributes as pixel features is computed. Directionally selective textural features are preferred primarily because of their ability to characterize singularities at multiple orientations, which often arise in carcinoma cell lines. A Support Vector Machine (SVM) classifier with Radial Basis Function (RBF) kernel is employed for final classification. Over a dataset of 280 images, we achieved an accuracy of 88.2%, which outperforms the classical correlation based methods. © 2012 IEEE.Item Open Access Contact guidance enhances the quality of a tissue engineered corneal stroma(John Wiley & Sons, Inc., 2008) Vrana, E.; Builles, N.; Hindie, M.; Damour O.; Aydınlı, Atilla; Hasirci, V.Corneal stroma is a very complex structure, composed of 200 lamellae of oriented collagen fibers. This highly complex nature of cornea is known to be important for its transparency and mechanical integrity. Thus, an artificial cornea design has to take into account this complex structure. In this study, behavior of human corneal keratocytes on collagen films patterned with parallel channels was investigated. Keratocytes proliferated well on films and reached confluency after 7 days in the incubation medium. Nearly all of the cells responded to the patterns and were aligned in contrast to the cells on unpatterned surfaces. Collagen type I and keratan sulfate secreted by keratocytes on patterned films appeared to be aligned in the direction of the patterns. The films showed an intermediate degradation over the course of a month. On the whole, transparency of the films increased with degradation and decreased by the presence of the cells. The decrease was, however, low and transparency level was maintained on the patterned films while on the unpatterned films a sharp decrease in transparency was followed by an improvement. This was due to the more organized distribution of cells and the oriented secretion of extracellular matrix molecules on patterned collagen films. Thus, these results suggest that application of contact guidance in cornea tissue engineering may facilitate the remodeling process, hence decrease the rehabilitation period.Item Open Access Cornea engineering on polyester carriers(John Wiley & Sons, Inc., 2006) Zorlutuna, P.; Tezcaner, A.; Kiyat, I.; Aydınlı, Atilla; Hasirci, V.In this study, biodegradable polyester based carriers were designed for tissue engineering of the epithelial and the stromal layers of the cornea, and the final construct was tested in vitro. In the construction of the epithelial layer, micropatterned films were prepared from blends of biodegradable and biocompatible polyesters of natural (PHBV) and synthetic (P(L/DL)LA) origin, and these films were seeded with D407 (retinal pigment epithelial) cells. To improve cell adhesion and growth, the films were coated with fibronectin. To serve as the stromal layer of the cornea, highly porous foams of P(L/DL)LA-PHBV blends were seeded with 3T3 fibroblasts. Cell numbers on the polyester carriers were significantly higher than those on the tissue culture polystyrene control. The cells and the carriers were characterized scanning electron micrographs showed that the foam was highly porous and the pores were interconnected. 3T3 Fibroblasts were distributed quite homogeneously at the seeding site, but probably because of the high thickness of the carrier (∼6 mm); they could not sufficiently populate the core (central parts of the foam) during the test duration. The D407 cells formed multilayers on the micropatterned polyester film. Immunohistochemical studies showed that the cells retained their phenotype during culturing; D407 cells formed tight junctions characteristic of epithelial cells, and 3T3 cells deposited collagen type I into the foams. On the basis of these results, we concluded that the micropatterned films and the foams made of P(L/DL)LA-PHBV blends have a serious potential as tissue engineering carriers for the reconstruction of the epithelial and stromal layers of the cornea.Item Open Access Designing circular CMUT cells using CMUT biasing chart(IEEE, 2012-10) Köymen, Hayrettin; Atalar, Abdullah; Oğuz, H. KağanA very accurate equivalent circuit model for circular CMUT cell is recently proposed. As a consequence of this model, the operating characteristics of the cell is derived and presented as a biasing chart for CMUTs. We discuss these operating characteristics and show how the coupling coefficient can be derived from the model. We present an analysis of receiver performance of a CMUT cell. We also demonstrate how to design cells for fixed bias voltage but for different static depression. © 2012 IEEE.Item Open Access Detection of Calcium-induced morphological changes on RBCs by digital holographic microscopy and blinking optical tweezers(IEEE, 2016) Rad, V. F.; Tavakkoli, R.; Moradi, Ali-Reza; Anand, A.; Javidi, B.Ca+2 level in the circulating red blood cells (RBCs) takes part not only in controlling biophysical properties, but also affects the membrane composition, and its morphological and rheological properties. Excessive accumulation of Ca2+ within the cells is associated with a number of important pathological diseases. In this paper, by the use of digital holographic microscopy (DHM), we quantitatively analyzed the volumetric behavior of RBC membrane under influence of excess Calcium ions. DHM in a transmission mode is an effective tool for quantitative visualization of phase objects. By deriving the associated phase changes 3D information on the morphology variation of the cells at arbitrary time scales is obtained. Individual cells are immobilized by the use of optical tweezers and are monitored live with DHM system, while the concentration of Ca2+ ions in the buffer is changed simultaneously. We utilized blinking optical tweezers, by inserting an optical chopper to modulate intensity of the trapping laser beam. Blinking optical tweezers, while keeping the cell trapped during the experiments, ensures of minimizing the photo-damage of trapping laser beam on the cell. Our experimental results are in agreement with previous biological studies and predictions, and experimental observations of living RBCs under Ca2+ influence.Item Open Access Encapsulation of two different TLR ligands into liposomes confer protective immunity and prevent tumor development(Elsevier B.V., 2017) Bayyurt, B.; Tincer, G.; Almacioglu, K.; Alpdundar, E.; Gursel, M.; Gursel, I.Nucleic acid-based Toll-like receptor (TLR) ligands are promising adjuvants and immunotherapeutic agents. Combination of TLR ligands potentiates immune response by providing synergistic immune activity via triggering different signaling pathways and may impact antigen dependent T-cell immune memory. However, their short circulation time due to nuclease attack hampers their clinical performance. Liposomes offer inclusion of protein and nucleic acid-based drugs with high encapsulation efficiency and drug loading. Furthermore, they protect cargo from enzymatic cleavage while providing stability, and enhancing biological activity. Herein, we aimed to develop a liposomal carrier system co-encapsulating TLR3 (polyinosinic-polycytidylic acid; poly(I:C)) and TLR9 (oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs; CpG ODN) ligands as immunoadjuvants together with protein antigen. To demonstrate that this depot system not only induce synergistic innate immune activation but also boost antigen-dependent immune response, we analyzed the potency of dual ligand encapsulated liposomes in long-term cancer protection assay. Data revealed that CpG ODN and poly(I:C) co-encapsulation significantly enhanced cytokine production from spleen cells. Activation and maturation of dendritic cells as well as bactericidal potency of macrophages along with internalization capacity of ligands were elevated upon incubation with liposomes co-encapsulating CpG ODN and poly(I:C). Immunization with co-encapsulated liposomes induced OVA-specific Th1-biased immunity which persisted for eight months post-booster injection. Subsequent challenge with OVA-expressing tumor cell line, E.G7, demonstrated that mice immunized with liposomes co-encapsulating dual ligands had significantly slower tumor progression. Tumor clearance was dependent on OVA-specific cytotoxic memory T-cells. These results suggest that liposomes co-encapsulating TLR3 and TLR9 ligands and a specific cancer antigen could be developed as a preventive cancer vaccine. � 2017 Elsevier B.V.Item Open Access Equivalent circuit-based analysis of CMUT cell dynamics in arrays(IEEE, 2013) Oğuz, H. K.; Atalar, Abdullah; Köymen, HayrettinCapacitive micromachined ultrasonic transducers (CMUTs) are usually composed of large arrays of closely packed cells. In this work, we use an equivalent circuit model to analyze CMUT arrays with multiple cells. We study the effects of mutual acoustic interactions through the immersion medium caused by the pressure field generated by each cell acting upon the others. To do this, all the cells in the array are coupled through a radiation impedance matrix at their acoustic terminals. An accurate approximation for the mutual radiation impedance is defined between two circular cells, which can be used in large arrays to reduce computational complexity. Hence, a performance analysis of CMUT arrays can be accurately done with a circuit simulator. By using the proposed model, one can very rapidly obtain the linear frequency and nonlinear transient responses of arrays with an arbitrary number of CMUT cells. We performed several finite element method (FEM) simulations for arrays with small numbers of cells and showed that the results are very similar to those obtained by the equivalent circuit model.Item Open Access Extracting the temperature distribution on a phase-change memory cell during crystallization(American Institute of Physics Inc., 2016-10) Bakan, G.; Gerislioglu, B.; Dirisaglik, F.; Jurado, Z.; Sullivan, L.; Dana, A.; Lam, C.; Gokirmak A.; Silva, H.Phase-change memory (PCM) devices are enabled by amorphization- and crystallization-induced changes in the devices' electrical resistances. Amorphization is achieved by melting and quenching the active volume using short duration electrical pulses (∼ns). The crystallization (set) pulse duration, however, is much longer and depends on the cell temperature reached during the pulse. Hence, the temperature-dependent crystallization process of the phase-change materials at the device level has to be well characterized to achieve fast PCM operations. A main challenge is determining the cell temperature during crystallization. Here, we report extraction of the temperature distribution on a lateral PCM cell during a set pulse using measured voltage-current characteristics and thermal modelling. The effect of the thermal properties of materials on the extracted cell temperature is also studied, and a better cell design is proposed for more accurate temperature extraction. The demonstrated study provides promising results for characterization of the temperature-dependent crystallization process within a cell.Item Open Access Glycosaminoglycan-Mimetic Signals Direct the Osteo/Chondrogenic Differentiation of Mesenchymal Stem Cells in a Three-Dimensional Peptide Nanofiber Extracellular Matrix Mimetic Environment(American Chemical Society, 2016-02) Arslan, E.; Güler, Mustafa O.; Tekinay, A. B.Recent efforts in bioactive scaffold development focus strongly on the elucidation of complex cellular responses through the use of synthetic systems. Designing synthetic extracellular matrix (ECM) materials must be based on understanding of cellular behaviors upon interaction with natural and artificial scaffolds. Hence, due to their ability to mimic both the biochemical and mechanical properties of the native tissue environment, supramolecular assemblies of bioactive peptide nanostructures are especially promising for development of bioactive ECM-mimetic scaffolds. In this study, we used glycosaminoglycan (GAG) mimetic peptide nanofiber gel as a three-dimensional (3D) platform to investigate how cell lineage commitment is altered by external factors. We observed that amount of fetal bovine serum (FBS) presented in the cell media had synergistic effects on the ability of GAG-mimetic nanofiber gel to mediate the differentiation of mesenchymal stem cells into osteogenic and chondrogenic lineages. In particular, lower FBS concentration in the culture medium was observed to enhance osteogenic differentiation while higher amount FBS promotes chondrogenic differentiation in tandem with the effects of the GAG-mimetic 3D peptide nanofiber network, even in the absence of externally administered growth factors. We therefore demonstrate that mesenchymal stem cell differentiation can be specifically controlled by the combined influence of growth medium components and a 3D peptide nanofiber environment.Item Open Access In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction(Lippincott Williams & Wilkins, 2003) Kraitchman, D. L.; Heldman, A. W.; Atalar, Ergin; Amado, L. C.; Martin, B. J.; Pittenger, M. F.; Hare, J. M.; Bulte, J. W. M.Background - We investigated the potential of magnetic resonance imaging (MRI) to track magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model. Methods and Results - Adult farm pigs (n=5) were subjected to closed-chest experimental MI. MR-MSCs (2.8 to 16×107 cells) were injected intramyocardially under x-ray fluoroscopy. MRIs were obtained on a 1.5T MR scanner to demonstrate the location of the MR-MSCs and were correlated with histology. Contrast-enhanced MRI demonstrated successful injection in the infarct and serial MSC tracking was demonstrated in two animals. Conclusion - MRI tracking of MSCs is feasible and represents a preferred method for studying the engraftment of MSCs in MI.Item Open Access A microfluidic erythrocyte sedimentation rate analyzer using rouleaux formation kinetics(Springer Verlag, 2017-03) Isiksacan, Z.; Asghari, M.; Elbuken, C.Red blood cell aggregation is an intrinsic property of red blood cells that form reversible stacked structures, also called rouleaux, under low shear rates. Erythrocyte sedimentation rate (ESR), commonly performed in clinics, is an indirect inflammation screener and a prognostic test for diseases. We have recently developed a microfluidic system for rapid measurement of ESR from 40 µl whole blood employing the aggregation dynamics. In this work, we propose the use of an aggregation inducer, dextran polyglucose, for the preparation of multiple blood samples with differing aggregation dynamics. Using these samples, we characterized the performance of the system with three aggregation indices and under varying experimental conditions. Additionally, using the same underlying principle, we improved the system for ESR measurement using both venipuncture and fingerprick whole blood samples depending on the user needs. The results demonstrate that the system performs equally well with both samples, which validates the compatibility of the system for both laboratory and point-of-care applications where venous and capillary blood are the primary samples, respectively. The detailed characterization presented in this study legitimates the feasibility of the system for ultrafast and facile measurement of ESR in clinics and diverse off-laboratory settings.Item Open Access Microsphere-Assisted Super-Resolved Mirau Digital Holographic Microscopy for Cell Identification(OSA - The Optical Society, 2017) Aakhte, M.; Abbasian, V.; Akhlaghi, E. A.; Moradi, A. R.; Anand, A.; Javidi, B.In this paper, we use a glass microsphere incorporated into a digital holographic microscope to increase the effective resolution of the system, aiming at precise cell identification. A Mirau interferometric objective is employed in the experiments, which can be used for a common-path digital holographic microscopy (DHMicroscopy) arrangement. High-magnification Mirau objectives are expensive and suffer from low working distances, yet the commonly used low-magnification Mirau objectives do not have high lateral resolutions. We show that by placing a glass microsphere within the working distance of a low-magnification Mirau objective, its effective numerical aperture can be increased, leading to super-resolved three-dimensional images. The improvement in the lateral resolution depends on the size and vertical position of microsphere, and by varying these parameters, the lateral resolution and magnification may be adjusted. We used the information from the super-resolution DHMicroscopy to identify thalassemia minor red blood cells (tRBCs). Identification is done by comparing the volumetric measurements with those of healthy RBCs. Our results show that microsphere-assisted super-resolved Mirau DHMicroscopy, being common path and off-axis in nature, has the potential to serve as a benchtop device for cell identification and biomedical measurements.Item Open Access Morphology-tailored synthesis of tungsten trioxide (Hydrate) thin films and their photocatalytic properties(ACS Publications, 2011-01-10) Jiao, Z. H.; Wang, J. M.; Ke, L.; Sun, X. W.; Demir, Hilmi VolkanTungsten trioxide hydrate (3WO(3)center dot H(2)O) films with different morphologies were directly grown on fluorine doped tin oxide (FTO) subsi:rate via a facile crystal-seed-assisted hydrothermal method. Scanning electron microscopy (SEM) analysis showed that 3WO(3)center dot H(2)O thin films composed of platelike, wedgelike, and sheetlike nanostructures could be selectively synthesized by adding Na(2)SO(4), (NH(4))(2)SO(4), and CH(3)COONH(4) as capping agents, respectively. X-ray diffraction (XRD) studies indicated that these films were of orthorhombic structure. The as-prepared thin films after dehydration showed obvious photcicatalytic activities. The best film grown using CH(3)COONH(4) as a capping agent generated anodic photocurrents of 1.16 mA/cm(2) fork oxidization of methanol and 0.5 mA/cm(2) for water splitting with the highest photoconversion efficiency of about 0.3% under simulated solar illumination.