PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - WoS: 14Lamin A/C Is Dispensable To Mechanical Repression of Adipogenesis(MDPI, 2021) Goelzer, Matthew; Dudakovic, Amel; Olçum, Melis; Sen, Buer; Özçivici, Engin; Rubin, Janet; van Wijnen, Andre J.Mesenchymal stem cells (MSCs) maintain the musculoskeletal system by differentiating into multiple lineages, including osteoblasts and adipocytes. Mechanical signals, including strain and low-intensity vibration (LIV), are important regulators of MSC differentiation via control exerted through the cell structure. Lamin A/C is a protein vital to the nuclear architecture that supports chromatin organization and differentiation and contributes to the mechanical integrity of the nucleus. We investigated whether lamin A/C and mechanoresponsiveness are functionally coupled during adipogenesis in MSCs. siRNA depletion of lamin A/C increased the nuclear area, height, and volume and decreased the circularity and stiffness. Lamin A/C depletion significantly decreased markers of adipogenesis (adiponectin, cellular lipid content) as did LIV treatment despite depletion of lamin A/C. Phosphorylation of focal adhesions in response to mechanical challenge was also preserved during loss of lamin A/C. RNA-seq showed no major adipogenic transcriptome changes resulting from LIV treatment, suggesting that LIV regulation of adipogenesis may not occur at the transcriptional level. We observed that during both lamin A/C depletion and LIV, interferon signaling was downregulated, suggesting potentially shared regulatory mechanism elements that could regulate protein translation. We conclude that the mechanoregulation of adipogenesis and the mechanical activation of focal adhesions function independently from those of lamin A/C.Article Citation - WoS: 21Citation - Scopus: 22Daily Application of Low Magnitude Mechanical Stimulus Inhibits the Growth of Mda-Mb Breast Cancer Cells in Vitro(BioMed Central Ltd., 2014) Ölçüm, Melis; Özçivici, EnginIntroduction: Mechanical loads can regulate cell proliferation and differentiation at various stages of development and homeostasis. However, the extension of this regulatory effect of mechanical loads on cancer cells is largely unknown. Increased physical compliance is one of the key features of cancer cells, which may hamper the transmission of mechanical loads to these cells within tumor microenvironment. Here we tested whether brief daily application of an external low magnitude mechanical stimulus (LMMS), would impede the growth of MDA-MB-231 aggressive type breast cancer cells in vitro for 3 wks of growth. Methods: The signal was applied in oscillatory form at 90 Hz and 0.15 g, a regimen that would induce mechanical loads on MDA-MB-231 cells via inertial properties of cells rather than matrix deformations. Experimental cells were exposed to LMMS 15 min/day, 5 days/week in ambient conditions while control cells were sham loaded. Cell proliferation, viability, cycle, apoptosis, morphology and migration were tested via Trypan Blue dye exclusion, MTT, PI, Annexin V, Calcein-AM and phalloidin stains and scratch wound assays. Results: Compared to sham controls, daily application of LMMS reduced the number and viability of cancerous MDA-MB-231 cells significantly after first week in the culture, while non-cancerous MCF10A cells were found to be unaffected. Flow cytomety analyses suggested that the observed decrease for the cancer cells in the LMMS group was due to a cell cycle arrest rather than apoptosis. LMMS further reduced cancer cell circularity and increased cytoskeletal actin in MDA-MB-231 cells. Conclusion: Combined, results suggest that direct application of mechanical loads negatively regulate the proliferation of aggressive type cancer cells. If confirmed, this non-invasive approach may be integrated to the efforts for the prevention and/or treatment of cancer.Article Citation - WoS: 79Citation - Scopus: 93Magnetic Force-Based Micro Fluidic Techniques for Cellular and Tissue Bioengineering(Frontiers Media S.A., 2018) Yaman, Sena; Anıl İnevi, Müge; Özçivici, Engin; Tekin, Hüseyin CumhurLive cell manipulation is an important biotechnological tool for cellular and tissue level bioengineering applications due to its capacity for guiding cells for separation, isolation, concentration, and patterning. Magnetic force-based cell manipulation methods offer several advantages, such as low adverse effects on cell viability and low interference with the cellular environment. Furthermore, magnetic-based operations can be readily combined with microfluidic principles by precisely allowing control over the spatiotemporal distribution of physical and chemical factors for cell manipulation. In this review, we present recent applications of magnetic force-based cell manipulation in cellular and tissue bioengineering with an emphasis on applications with microfluidic components. Following an introduction of the theoretical background of magnetic manipulation, components of magnetic force-based cell manipulation systems are described. Thereafter, different applications, including separation of certain cell fractions, enrichment of rare cells, and guidance of cells into specific macro- or micro-arrangements to mimic natural cell organization and function, are explained. Finally, we discuss the current challenges and limitations of magnetic cell manipulation technologies in microfluidic devices with an outlook on future developments in the field.Article Citation - WoS: 79Citation - Scopus: 94Biofabrication of in Situ Self Assembled 3d Cell Cultures in a Weightlessness Environment Generated Using Magnetic Levitation(Nature Publishing Group, 2018) Anıl İnevi, Müge; Yaman, Sena; Arslan Yıldız, Ahu; Meşe, Gülistan; Yalçın Özuysal, Özden; Tekin, Hüseyin Cumhur; Özçivici, EnginMagnetic levitation though negative magnetophoresis is a novel technology to simulate weightlessness and has recently found applications in material and biological sciences. Yet little is known about the ability of the magnetic levitation system to facilitate biofabrication of in situ three dimensional (3D) cellular structures. Here, we optimized a magnetic levitation though negative magnetophoresis protocol appropriate for long term levitated cell culture and developed an in situ 3D cellular assembly model with controlled cluster size and cellular pattern under simulated weightlessness. The developed strategy outlines a potential basis for the study of weightlessness on 3D living structures and with the opportunity for real-time imaging that is not possible with current ground-based simulated weightlessness techniques. The low-cost technique presented here may offer a wide range of biomedical applications in several research fields, including mechanobiology, drug discovery and developmental biology.Article Citation - WoS: 57Citation - Scopus: 61Viewpoints: Feeding Mechanics, Diet, and Dietary Adaptations in Early Hominins(John Wiley and Sons Inc., 2013) Daegling, David J.; Judex, Stefan; Özçivici, Engin; Ravosa, Matthew J.; Taylor, Andrea B.; Grine, Frederick E.; Teaford, Mark F.; Ungar, Peter S.Inference of feeding adaptation in extinct species is challenging, and reconstructions of the paleobiology of our ancestors have utilized an array of analytical approaches. Comparative anatomy and finite element analysis assist in bracketing the range of capabilities in taxa, while microwear and isotopic analyses give glimpses of individual behavior in the past. These myriad approaches have limitations, but each contributes incrementally toward the recognition of adaptation in the hominin fossil record. Microwear and stable isotope analysis together suggest that australopiths are not united by a single, increasingly specialized dietary adaptation. Their traditional (i.e., morphological) characterization as "nutcrackers" may only apply to a single taxon, Paranthropus robustus. These inferences can be rejected if interpretation of microwear and isotopic data can be shown to be misguided or altogether erroneous. Alternatively, if these sources of inference are valid, it merely indicates that there are phylogenetic and developmental constraints on morphology. Inherently, finite element analysis is limited in its ability to identify adaptation in paleobiological contexts. Its application to the hominin fossil record to date demonstrates only that under similar loading conditions, the form of the stress field in the australopith facial skeleton differs from that in living primates. This observation, by itself, does not reveal feeding adaptation. Ontogenetic studies indicate that functional and evolutionary adaptation need not be conceptually isolated phenomena. Such a perspective helps to inject consideration of mechanobiological principles of bone formation into paleontological inferences. Finite element analysis must employ such principles to become an effective research tool in this context. © 2013 Wiley Periodicals, Inc.Article Citation - WoS: 18Citation - Scopus: 21Genetic Loci That Control the Loss and Regain of Trabecular Bone During Unloading and Reambulation(John Wiley and Sons Inc., 2013) Judex, Stefan; Zhang, Weidong; Donahue, Leah Rae; Özçivici, EnginChanges in trabecular morphology during unloading and reloading are marked by large variations between individuals, implying that there is a strong genetic influence on the magnitude of the response. Here, we subjected more than 350 second-generation (BALBxC3H) 4-month-old adult female mice to 3 weeks of hindlimb unloading followed by 3 weeks of reambulation to identify the quantitative trait loci (QTLs) that define an individual's propensity to either lose trabecular bone when weight bearing is removed or to gain trabecular bone when weight bearing is reintroduced. Longitudinal in vivo micro-computed tomography (μCT) scans demonstrated that individual mice lost between 15% and 71% in trabecular bone volume fraction (BV/TV) in the distal femur during unloading (average: -43%). Changes in trabecular BV/TV during the 3-week reambulation period ranged from a continuation of bone loss (-18%) to large additions (56%) of tissue (average: +10%). During unloading, six QTLs accounted for 21% of the total variability in changes in BV/TV whereas one QTL accounted for 6% of the variability in changes in BV/TV during reambulation. QTLs were also identified for changes in trabecular architecture. Most of the QTLs defining morphologic changes during unloading or reambulation did not overlap with those QTLs identified at baseline, suggesting that these QTLs harbor genes that are specific for sensing changes in the levels of weight bearing. The lack of overlap in QTLs between unloading and reambulation also emphasizes that the genes modulating the trabecular response to unloading are distinct from those regulating tissue recovery during reloading. The identified QTLs contain the regulatory genes underlying the strong genetic regulation of trabecular bone's sensitivity to weight bearing and may help to identify individuals that are most susceptible to unloading-induced bone loss and/or the least capable of recovering.