Publications with Fulltext
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
Browse
84 results
Search Results
Publication Open Access Multifunctional alginate-based hydrogel with reversible crosslinking for controlled therapeutics delivery(Elsevier, 2020) Ekinci, Duygu; N/A; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Batool, Syeda Rubab; Nazeer, Muhammad Anwaar; Kızılel, Seda; Şahin, Afsun; PhD Student; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; College of Engineering; School of Medicine; N/A; N/A; 28376; 171267Glycan-based alginate hydrogels have great potential in creating new vehicles with responsive behavior and tunable properties for biomedicine. However, precise control and tunability in properties present major barrier for clinical translation of these materials. Here, we report the synthesis of pH responsive anthracene modified glycan-based hydrogels for selective release of therapeutic molecules. Hydrogels were crosslinked through simultaneous photopolymerization of vinyl groups and photodimerization of anthracene. Incorporation of anthracene into these gels leads to reversible control on crosslinking and transition between gel/sol states through dimerization/dedimerization of anthracene groups. Chemotherapeutic drug doxorubicin-loaded hydrogels were then tested in a cancer mimetic microenvironment where 85% of the drug was released from anthracene-conjugated hydrogels at pH 2 for 6 days. Control on gelation with anthracene incorporation was observed through alterations in modulus, where storage modulus was increased two-fold with anthracene conjugation during photopolymerization and photodimerization. Furthermore, cell survival analysis revealed that anthracene conjugation could selectively compromise cancer cell viability without inducing significant toxicity on healthy fibroblasts. This study combines light-induced control of crosslink density due to anthracene and pH-triggered therapeutics delivery with alginate. The approach would be applicable for systems where multiple control is required with high precision.Publication Open Access The structural basis of Akt PH domain interaction with calmodulin(Elsevier, 2021) Jang, Hyunbum; Nussinov, Ruth; N/A; Department of Chemical and Biological Engineering; Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Computer Engineering; Weako, Jackson; Keskin, Özlem; Gürsoy, Attila; Faculty Member; Graduate School of Sciences and Engineering; College of Engineering; N/A; 26605; 8745Akt plays a key role in the Ras/PI3K/Akt/mTOR signaling pathway. In breast cancer, Akt translocation to the plasma membrane is enabled by the interaction of its pleckstrin homology domain (PHD) with calmodulin (CaM). At the membrane, the conformational change promoted by PIP3 releases CaM and facilitates Thr308 and Ser473 phosphorylation and activation. Here, using modeling and molecular dynamics simulations, we aim to figure out how CaM interacts with Akt's PHD at the atomic level. Our simulations show that CaM-PHD interaction is thermodynamically stable and involves a beta-strand rather than an alpha-helix, in agreement with NMR data, and that electrostatic and hydrophobic interactions are critical. The PHD interacts with CaM lobes; however, multiple modes are possible. IP4, the polar head of PIP3, weakens the CaM-PHD interaction, implicating the release mechanism at the plasma membrane. Recently, we unraveled the mechanism of PI3K alpha activation at the atomistic level and the structural basis for Ras role in the activation. Here, our atomistic structural data clarify the mechanism of how CaM interacts, delivers, and releases Akt-the next node in the Ras/PI3K pathway-at the plasma membrane.Publication Open Access Improving CO2 separation performance of MIL-53(Al) by incorporating 1-N-Butyl-3-methylimidazolium methyl sulfate(Wiley, 2019) Department of Chemical and Biological Engineering; N/A; Department of Chemical and Biological Engineering; Kulak, Harun; Polat, Hüsamettin Mert; Kavak, Safiyye; Keskin, Seda; Uzun, Alper; Faculty Member; 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; N/A; N/A; N/A; 40548; 599171-n-Butyl-3-methylimidazolium methyl sulfate is incorporated into MIL-53(Al). Detailed characterization is done by X-ray fluorescence, Brunauer-Emmett-Teller surface area, scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. Results show that ionic liquid (IL) interacts directly with the framework, significantly modifying the electronic environment of MIL-53(Al). Based on the volumetric gas adsorption measurements, CO2, CH4, and N-2 adsorption capacities decreased from 112.0, 46.4, and 19.6 cc (STP) g(MIL-53(Al))(-1) to 42.2, 13.0, and 4.3 cc (STP) g(MIL-53(Al))(-1) at 5 bar, respectively, upon IL incorporation. Data show that this postsynthesis modification leads to more than two and threefold increase in the ideal selectivity for CO2 over CH4 and N-2 separations, respectively, as compared with pristine MIL-53(Al). The isosteric heat of adsorption (Qst) values show that IL incorporation increases CO2 affinity and decreases CH4 and N-2 affinities. Cycling adsorption-desorption measurements show that the composite could be regenerated with almost no decrease in the CO2 adsorption capacity for six cycles and confirm the lack of any significant IL leaching. The results offer MIL-53(Al) as an excellent platform for the development of a new class of IL/MOF composites with exceptional performance for CO2 separation.Publication Open Access SimMBM channel simulator for media-based modulation systems(Institute of Electrical and Electronics Engineers (IEEE), 2021) Yiğit Zehra; Altunbaş, İbrahim; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Başar, Ertuğrul; Faculty Member; College of Engineering; 149116Media-based modulation (MBM), exploiting rich scattering properties of transmission environments via different radiation patterns of a single reconfigurable antenna (RA), has brought new insights into future communication systems. In this study, considering this innovative transmission principle, we introduce the realistic, two-dimensional (2D), and open-source SimMBM channel simulator to support various applications of MBM systems at sub-6 GHz frequency band in different environments.Publication Open Access Engineering human stellate cells for beta cell replacement therapy promotes in vivo recruitment of regulatory T cells(Elsevier, 2019) N/A; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Oran, Dilem Ceren; Lokumcu, Tolga; Bal, Tuğba; İnceoğlu, Yasemin; Albayrak, Özgür; Erkan, Murat Mert; Kurtoğlu, Metin; Can, Füsun; Önder, Tuğba Bağcı; Kızılel, Seda; Akolpoğlu, Mükrime Birgül; Faculty Member; Faculty Member; Master Student; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; Graduate School of Health Sciences; College of Engineering; School of Medicine; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 103165; 184359; 28376; N/AType 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic β cells. One of the promising therapeutic approaches in T1D is the transplantation of islets; however, it has serious limitations. To address these limitations, immunotherapeutic strategies have focused on restoring immunologic tolerance, preventing transplanted cell destruction by patients’ own immune system. Macrophage-derived chemokines such as chemokine-ligand-22 (CCL22) can be utilized for regulatory T cell (Treg) recruitment and graft tolerance. Stellate cells (SCs) have various immunomodulatory functions: recruitment of Tregs and induction of T-cell apoptosis. Here, we designed a unique immune-privileged microenvironment around implantable islets through overexpression of CCL22 proteins by SCs. We prepared pseudoislets with insulin-secreting mouse insulinoma-6 (MIN6) cells and human SCs as a model to mimic naive islet morphology. Our results demonstrated that transduced SCs can secrete CCL22 and recruit Tregs toward the implantation site in vivo. This study is promising to provide a fundamental understanding of SC-islet interaction and ligand synthesis and transport from SCs at the graft site for ensuring local immune tolerance. Our results also establish a new paradigm for creating tolerable grafts for other chronic diseases such as diabetes, anemia, and central nervous system (CNS) diseases, and advance the science of graft tolerance.Publication Open Access Predicting important residues and ınteraction pathways in proteins using Gaussian network model: binding and stability of HLA proteins(Public Library of Science, 2010) Haliloğlu, Türkan; Gül, Ahmet; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Erman, Burak; Faculty Member; College of Engineering; 179997A statistical thermodynamics approach is proposed to determine structurally and functionally important residues in native proteins that are involved in energy exchange with a ligand and other residues along an interaction pathway. The structure-function relationships, ligand binding and allosteric activities of ten structures of HLA Class I proteins of the immune system are studied by the Gaussian Network Model. Five of these models are associated with inflammatory rheumatic disease and the remaining five are properly functioning. In the Gaussian Network Model, the protein structures are modeled as an elastic network where the inter-residue interactions are harmonic. Important residues and the interaction pathways in the proteins are identified by focusing on the largest eigenvalue of the residue interaction matrix. Predicted important residues match those known from previous experimental and clinical work. Graph perturbation is used to determine the response of the important residues along the interaction pathway. Differences in response patterns of the two sets of proteins are identified and their relations to disease are discussed.Publication Open Access Observation of the correlations between pair wise interaction and functional organization of the proteins, in the protein ınteraction network of saccaromyces cerevisiae(World Academy of Science, Engineering and Technology (WASET), 2008) Haliloğlu, T.; Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Computer Engineering; Department of Chemical and Biological Engineering; Tunçbağ, Nurcan; Keskin, Özlem; Faculty Member; College of Engineering; N/A; 26605Understanding the cell's large-scale organization is an interesting task in computational biology. Thus, protein-protein interactions can reveal important organization and function of the cell. Here, we investigated the correspondence between protein interactions and function for the yeast. We obtained the correlations among the set of proteins. Then these correlations are clustered using both the hierarchical and biclustering methods. The detailed analyses of proteins in each cluster were carried out by making use of their functional annotations. As a result, we found that some functional classes appear together in almost all biclusters. On the other hand, in hierarchical clustering, the dominancy of one functional class is observed. In brief, from interaction data to function, some correlated results are noticed about the relationship between interaction and function which might give clues about the organization of the proteins.Publication Open Access Nanoengineering InP quantum dot-based photoactive biointerfaces for optical control of neurons(Frontiers, 2021) Ulgut, Burak; Department of Electrical and Electronics Engineering; Department of Chemical and Biological Engineering; N/A; Department of Electrical and Electronics Engineering; Department of Chemical and Biological Engineering; Nizamoğlu, Sedat; Kavaklı, İbrahim Halil; Şahin, Afsun; Karatüm, Onuralp; Aria, Mohammad Mohammadi; Eren, Güncem Özgün; Yıldız, Erdost; Melikov, Rustamzhon; Srivastava, Shashi Bhushan; Sürme, Saliha; Doğru-Yüksel, Itır Bakış; Jalali, Houman Bahmani; Faculty Member; Faculty Member; Faculty Member; PhD Student; Researcher; Teaching Faculty; PhD Student; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; School of Medicine; Graduate School of Sciences and Engineering; Graduate School of Health Sciences; 130295; 40319; 171267; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/ALight-activated biointerfaces provide a non-genetic route for effective control of neural activity. InP quantum dots (QDs) have a high potential for such biomedical applications due to their uniquely tunable electronic properties, photostability, toxic-heavy-metal-free content, heterostructuring, and solution-processing ability. However, the effect of QD nanostructure and biointerface architecture on the photoelectrical cellular interfacing remained unexplored. Here, we unravel the control of the photoelectrical response of InP QD-based biointerfaces via nanoengineering from QD to device-level. At QD level, thin ZnS shell growth (similar to 0.65 nm) enhances the current level of biointerfaces over an order of magnitude with respect to only InP core QDs. At device-level, band alignment engineering allows for the bidirectional photoelectrochemical current generation, which enables light-induced temporally precise and rapidly reversible action potential generation and hyperpolarization on primary hippocampal neurons. Our findings show that nanoengineering QD-based biointerfaces hold great promise for next-generation neurostimulation devices.Publication Open Access HotRegion: a database of predicted hot spot clusters(Oxford University Press (OUP), 2012) N/A; Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Computer Engineering; Department of Chemical and Biological Engineering; Çukuroğlu, Engin; Gürsoy, Attila; Keskin, Özlem; PhD Student; Faculty Member; Graduate School of Sciences and Engineering; College of Engineering; N/A; 8745; 26605Hot spots are energetically important residues at protein interfaces and they are not randomly distributed across the interface but rather clustered. These clustered hot spots form hot regions. Hot regions are important for the stability of protein complexes, as well as providing specificity to binding sites. We propose a database called HotRegion, which provides the hot region information of the interfaces by using predicted hot spot residues, and structural properties of these interface residues such as pair potentials of interface residues, accessible surface area (ASA) and relative ASA values of interface residues of both monomer and complex forms of proteins. Also, the 3D visualization of the interface and interactions among hot spot residues are provided.Publication Open Access Assembly of huntingtin headpiece into α-helical bundles(American Institute of Physics (AIP) Publishing, 2017) Department of Mechanical Engineering; Department of Chemical and Biological Engineering; Department of Mechanical Engineering; Department of Chemical and Biological Engineering; Özgür, Beytullah; Sayar, Mehmet; PhD Student; Faculty Member; Graduate School of Sciences and Engineering; College of Engineering; College of Sciences; N/A; 109820Protein aggregation is a hallmark of neurodegenerative disorders. In this group of brain-related disorders, a disease-specific “host” protein or fragment misfolds and adopts a metastatic, aggregate-prone conformation. Often, this misfolded conformation is structurally and thermodynamically different from its native state. Intermolecular contacts, which arise in this non-native state, promote aggregation. In this regard, understanding the molecular principles and mechanisms that lead to the formation of such a non-native state and further promote the formation of the critical nucleus for fiber growth is essential. In this study, the authors analyze the aggregation propensity of Huntingtin headpiece (httNT), which is known to facilitate the polyQ aggregation, in relation to the helix mediated aggregation mechanism proposed by the Wetzel group. The authors demonstrate that even though httNT displays a degenerate conformational spectrum on its own, interfaces of macroscopic or molecular origin can promote the α-helix conformation, eliminating all other alternatives in the conformational phase space. Our findings indicate that httNT molecules do not have a strong orientational preference for parallel or antiparallel orientation of the helices within the aggregate. However, a parallel packed bundle of helices would support the idea of increased polyglutamine concentration, to pave the way for cross-β structures.