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Publication Metadata only Analysis of hot region organization in hub proteins(Springer, 2010) N/A; Department of Computer Engineering; Department of Chemical and Biological Engineering; Çukuroğlu, Engin; Gürsoy, Attila; Keskin, Özlem; PhD Student; Faculty Member; Faculty Member; Department of Computer Engineering; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 8745; 26605Protein interaction maps constructed from binary interactions reveal that some proteins are highly connected to others (acting as hub proteins), whereas some others have a few interactions (at the edges of the map). This paper addresses hub proteins from a structural point: interfaces. It investigates how hot spots are organized in hub proteins (hot regions). We annotate interfaces as the ones between two date-hubs (DD), two party hubs (PP), and two non-hubs (NN). We investigate the physico-chemical properties of these three types of interfaces focusing on the accessible surface area distribution, hot region organization, and amino acid composition differences. Results reveal that there are significant differences between DD and PP interfaces. More of the hot spots are organized into the hot regions in DD interfaces compared to PP ones. A high fraction of the interfaces are covered by hot regions in DD interfaces. There are more distinct hot regions in DDs. Since the same (or overlapping) DD interfaces should be used repeatedly, different hot regions can be used to bind to different partners. Further, these hot region characteristics can be used to predict whether a given hub interface is involved in a DD or a PP interface type with 80% accuracy.Publication Metadata only Biosensing–drug delivery systems for in vivo applications(Elsevier, 2019) Erkoc, Pelin; N/A; N/A; Department of Chemical and Biological Engineering; Akolpoğlu, Mükrime Birgül; Bozüyük, Uğur; Kızılel, Seda; Master Student; PhD Student; Faculty Member; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 28376Early detection of diseases can increase the efficiency of therapies. Recent advances in biosensor technology have led to the development of accurate and robust systems that can sense disease-dependent changes in analyte. These advancements have enabled faster diagnosis and treatment for various diseases. The invention of smart-responsive materials has opened new gates for next-generation biosensors, which can release the therapeutic payload upon environmental changes. These integrated systems provide increased therapeutic efficacy with reduced side effects, and a better perspective for biomedical applications. With further efforts, including comprehensive research and computational modeling, biosensing–drug delivery systems may become powerful tools for the treatment of chronic diseases.Publication Metadata only Characterization of protein release from poly(ethylene glycol) hydrogels with crosslink density gradients(Wiley, 2014) N/A; N/A; Department of Chemical and Biological Engineering; Bal, Tuğba; Kepsütlü, Burcu; Kızılel, Seda; PhD Student; Master Student; Faculty Member; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; 353534; N/A; 28376Transplantation of cells within poly(ethylene glycol) (PEG) hydrogel scaffolds as effective immunoisolation barriers is becoming increasingly important strategy for tissue engineering and regenerative medicine. In these applications, crosslink density of these membranes has significant effect on the control of diffusion of many biomolecules such as nutrients, cellular wastes, and hormones. When these networks are designed with crosslink density gradients, alterations in network structure may have an effect on biomolecule diffusivity. The goal of this work was to synthesize PEG hydrogels via surface initiated photopolymerization for use in applications involving physiological protein delivery and cell encapsulation. For this purpose, PEG hydrogels of differing crosslink density gradients were formed via surface initiated photopolymerization, and the diffusion of model proteins with various molecular weights were observed through these PEG hydrogel scaffolds with defined properties. Diffusion coefficients were on the order of 10(-7)-10(-8) cm(2)/s and protein diffusion time scales varied from 5 min to 30 h. The results confirm that synthetic PEG hydrogels with crosslink density gradients are promising for controlled release of bioactive molecules and for covalent incorporation of ligands to support cell viability. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 487-495, 2014.Publication Metadata only Controlled drug delivery through a novel PEG hydrogel encapsulated silica aerogel system(Wiley, 2012) N/A; N/A; N/A; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Giray, Seda; Bal, Tuğba; Kartal, Ayşe Meriç; Kızılel, Seda; Erkey, Can; Master Student; PhD Student; Master Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; N/A; N/A; N/A; College of Engineering; College of Engineering; N/A; 353534; N/A; 28376; 29633A novel composite material consisting of a silica aerogel core coated by a poly(ethylene) glycol (PEG) hydrogel was developed. The potential of this novel composite as a drug delivery system was tested with ketoprofen as a model drug due to its solubility in supercritical carbon dioxide. The results indicated that both drug loading capacity and drug release profiles could be tuned by changing hydrophobicity of aerogels, and that drug loading capacity increased with decreased hydrophobicity, while slower release rates were achieved with increased hydrophobicity. Furthermore, higher concentration of PEG diacrylate in the prepolymer solution of the hydrogel coating delayed the release of the drug which can be attributed to the lower permeability at higher PEG diacrylate concentrations. The novel composite developed in this study can be easily implemented to achieve the controlled delivery of various drugs and/or proteins for specific applications. (C) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.Publication Metadata only Encapsulation of pancreatic islets within nano-thin functional polyethylene glycol coatings for enhanced insulin secretion(Mary Ann Liebert, Inc, 2010) Scavone, Andrew; Liu, Xiang; Nothias, Jean-Manuel; Ostrega, Diane; WitkoWSKi, Piotr; Millis, Michael; Department of Chemical and Biological Engineering; Kızılel, Seda; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 28376Covalent attachment of polymers to cells and tissues could be used to solve a variety of problems associated with cellular therapies. Insulin-dependent diabetes mellitus is a disease resulting from the autoimmune destruction of the beta cells of the islets of Langerhans in the pancreas. Transplantation of islets into diabetic patients is an attractive form of treatment, provided that the islets could be protected from the host's immune system to prevent graft rejection, and smaller numbers of islets transplanted in smaller volumes could be sufficient to reverse diabetes. Therefore, a need exists to develop islet encapsulation strategies that minimize transplant volume. In this study, we demonstrate the formation of nano-thin, poly(ethylene glycol) (PEG)-rich functional conformal coatings on individual islets via layer-by-layer assembly technique. The surface of the islets is modified with biotin-PEG-N-hydroxysuccinimide (NHS), and the islets are further covered by streptavidin (SA) and biotin-PEG-peptide conjugates using the layer-by-layer method. An insulinotropic ligand, glucagon-like peptide-1 (GLP-1), is conjugated to biotin-PEG-NHS. The insulinotropic effect of GLP-1 is investigated through layer-by-layer encapsulation of islets using the biotin-PEG-GLP-1 conjugate. The effect of islet surface modification using the biotin-PEG-GLP-1 conjugate on insulin secretion in response to glucose challenge is compared via static incubation and dynamic perifusion assays. The results show that islets coated with the functional PEG conjugate are capable of secreting more insulin in response to high glucose levels compared to control islets. Finally, the presence of SA is confirmed by indirect fluorescent staining with SA-Cy3, and the presence of PEG-peptide on the surface of the islets after treatment with biotin-PEG-GLP-1 is confirmed by indirect fluorescent staining with biotin-PEG-fluorescein isothiocyanate (FITC) and separately with an anti-GLP-1 antibody. This work demonstrates the feasibility of treating pancreatic islets with reactive polymeric segments and provides the foundation for a novel means of potential immunoisolation. With this technique, it may be possible to encapsulate and/or modify islets before portal vein transplantation and reduce transplantation volume significantly, and promote islet viability and insulin secretion due to the presence of insulinotropic peptides on the islet surface. Layer-by-layer self-assembly of PEG-GLP-1 offers a unique approach to islet encapsulation to stimulate insulin secretion in response to high glucose levels.Publication Metadata only Immunological response of polysaccharide nanogel-incorporating PEG hydrogels in an in vivo diabetic model(Taylor & Francis, 2022) Sasaki, Yoshihiro; Akiyoshi, Kazunari; N/A; N/A; N/A; N/A; Department of Chemical and Biological Engineering; Bal, Tuğba; Karaoğlu, İsmail Can; Murat, Füsun Şevval; Yalçın, Esra; Kızılel, Seda; PhD Student; PhD Student; PhD Student; PhD Student; Faculty Member; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; 353534; N/A; N/A; N/A; 28376Cell-based therapies hold significant advantages in comparison with the traditional drug-based or injection-based treatments. However, for long-term functional cellular implants, immune acceptance must be established. To accomplish the acceptance of the implanted cells, various biomaterial systems have been studied. Nanogels have shown great potential for modulation of cellular microenvironments, acting as a physical barrier between the immune system and the implant. However, internalization of nano-scale materials by implanted cells is not desirable and is yet to be overcome. In this study, we incorporated acrylate modified cholesterol-bearing pullulan (CHPOA) nanogels into poly (ethylene glycol) diacrylate (PEGDA) hydrogels through covalent crosslinking, where we used visible light-induced photopolymerization. We characterized morphology and swelling properties of CHPOA incorporated PEG composite hydrogels using FE-SEM and gravimetric analysis. Also, we investigated the biocompatibility properties of composite hydrogels in vivo, where we used both healthy and diabetic mice. We induced diabetes in mice using a low dose streptozotocin (STZ) injections and implanted composite hydrogels in both diabetic and healthy mice through subcutaneous route. Immune cell infiltration of the retrieved tissue was examined through histological analysis, where we observed minimum immune response levels of 0-2 rareness, according to ISO standard of biological evaluation of medical devices. Our observation suggests that the composite hydrogel developed here can be used to introduce nanostructured domains into bulk hydrogels and that this system has potential to be used as immunologically acceptable composite material in cellular therapy without internalization of nanoparticles.Publication Metadata only Integrating molecular simulations with machine learning guides in the design and synthesis of [bmim][bf(4)]/mof composites for co(2)/n(2) separation(American Chemical Society, 2023) N/A; N/A; N/A; N/A; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Harman, Hilal Dağlar; Gülbalkan, Hasan Can; Habib, Nitasha; Durak, Özce; Uzun, Alper; Keskin, Seda; PhD Student; PhD Student; PhD Student; Undergraduate Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences; College of Engineering and Engineering; College of Engineering; N/A; N/A; N/A; N/A; 59917; 40548Considering the existence of a large number and variety of metal-organic frameworks (MOFs) and ionic liquids (ILs), assessing the gas separation potential of all possible IL/MOF composites by purely experimental methods is not practical. In this work, we combined molecular simulations and machine learning (ML) algorithms to computationally design an IL/MOF composite. Molecular simulations were first performed to screen approximately 1000 different composites of 1-n-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) with a large variety of MOFs for CO2 and N2 adsorption. The results of simulations were used to develop ML models that can accurately predict the adsorption and separation performances of [BMIM][BF4]/MOF composites. The most important features that affect the CO2/N2 selectivity of composites were extracted from ML and utilized to computationally generate an IL/MOF composite, [BMIM][BF4]/UiO-66, which was not present in the original material data set. This composite was finally synthesized, characterized, and tested for CO2/N2 separation. Experimentally measured CO2/N2 selectivity of the [BMIM][BF4]/UiO-66 composite matched well with the selectivity predicted by the ML model, and it was found to be comparable, if not higher than that of all previously synthesized [BMIM][BF4]/MOF composites reported in the literature. Our proposed approach of combining molecular simulations with ML models will be highly useful to accurately predict the CO2/N2 separation performances of any [BMIM][BF4]/MOF composite within seconds compared to the extensive time and effort requirements of purely experimental methods.Publication Metadata only Liposomes under shear: structure, dynamics, and drug delivery applications(Wiley-VCH, 2023) Department of Chemical and Biological Engineering; N/A; Şenses, Erkan; Karaz, Selcan; Faculty Member; Master Student; Department of Chemical and Biological Engineering; College of Engineering; Graduate School of Sciences and Engineering; 280298; N/AThe targeted delivery to specific locations while not causing damage to healthy tissues efficiently remains a challenge in drug delivery systems. Through addressing this issue, stimuli-responsive materials have been under investigation. As one of the fundamental forces associated with blood flow, shear stress is taken as an advantage to design shear-sensitive drug carriers. Although blood flow is modeled as laminar flow under normal conditions, in case of constrictions caused by endothelial shear stress, cardiovascular diseases, or angiogenesis due to tumor formation, local shear stress can dramatically increase. To date, shear-sensitive materials have been investigated under two main categories: shear-disaggregated and shear-deformed nanoparticles based on their structural mechanism after exposure to high-shear stress. Among them, liposomes are promising materials with their soft and deformable structure, high biocompatibility, controlled-release properties, and sensitivity to shear stress. Herein, in this review, the effects of shear stress on liposomes in terms of their structural changes, flow regimes, rheological properties, and drug delivery applications are discussed. It is believed that this work provides a basis for designing more effective drug delivery systems considering the complexity of the human body.Publication Metadata only Mesenchymal Stem Cells (MSCs) Improve Beta Cell Function within Biomimetic PEG Hydrogels(Mary Ann Liebert, Inc., 2015) Karaoz, E.; Department of Chemical and Biological Engineering; N/A; Kızılel, Seda; Bal, Tuğba; Faculty Member; PhD Student; Department of Chemical and Biological Engineering; College of Engineering; Graduate School of Sciences and Engineering; 28376; 353534N/APublication Metadata only Mesenchymal stem cells and ligand incorporation in biomimetic poly(ethylene glycol) hydrogels significantly improve insulin secretion from pancreatic islets(Wiley, 2017) Okçu, Alparslan; Duruksu, Gökhan; Karaöz, Erdal; N/A; N/A; Department of Chemical and Biological Engineering; Bal, Tuğba; Nazlı, Caner; Kızılel, Seda; PhD Student; PhD Student; Faculty Member; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; 353534; N/A; 28376The main goal of this study was to investigate pancreatic islet function with mesenchymal stem cells (MSCs) in a ligand-functionalized poly(ethylene glycol) (PEG) hydrogel for the treatment of type 1 diabetes (T1D). Rat bone marrow-derived MSCs (rBM-MSCs) were encapsulated within synthetic PEG hydrogel, and cell viability and apoptosis within this 3D environment was examined in detail. ATP content and caspase-3 activity of encapsulated MSCs showed that fibronectin-derived RGDS, laminin-derived IKVAV and/or insulinotropic glucagon-like peptide (GLP-1) were required to maintain MSC survival. Incorporation of these peptides into the hydrogel environment also improved pancreatic islet viability, where combinations of peptides had altered effects on islet survival. GLP-1 alone was the leading stimulator for insulin secretion. Cell adhesion peptides RGDS and IKVAV improved insulin secretion only when theywere used in combination, but could not surpass the effect of GLP-1.Further, when pancreatic islets were co-encapsulated with MSCs within synthetic PEG hydrogel, a two- fold increase in the stimulation index wasmeasured. Synergistic effects ofMSCs and peptideswere observed, with a seven-fold increase in the stimulation index. The results are promising and suggest that simultaneous incorporation ofMSCs and ECM-derived peptides and/or GLP-1 can improve pancreatic islet function in response to altered glucose levels in the physiological environment. Copyright (C) 2014 John Wiley & Sons, Ltd.