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Integrative Biology: Quantitative Biosciences From Nano to Macro

Christopher Walter, Joshua T Davis, Jairaj Mathur, Amit Pathak
In fibrosis and cancer, degradation of basement membrane (BM) and cell invasion are considered as key outcomes of a cellular transformation called epithelial-mesenchymal transition (EMT). Here, we pose a converse question - can preexisting physical defects in the BM matrix cause EMT in normal epithelial cells? On a BM-mimicking matrix of collagen-IV-coated polyacrylamide (PA) gel, we have discovered a reverse phenomenon in which preexisting defects trigger EMT in normal epithelial cells. Through spatiotemporal measurements and simulations in silico, we demonstrate that the EMT precedes cellular mechanoactivation on defective matrices, but they occur concurrently on stiff matrices...
May 23, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Eleonora Grespan, Giovanni G Giobbe, Florent Badique, Karine Anselme, Jürgen Rühe, Nicola Elvassore
Mechanical stimuli and geometrical constraints transmitted across the cytoskeleton to the nucleus affect the nuclear morphology and cell function. Human pluripotent stem cells (hPSCs) represent an effective tool for evaluating transitions in nuclear deformability from the pluripotent to differentiated stage, and for deciphering the underlying mechanisms. We report the first study that investigates the nuclear deformability induced by geometrical constraints of hPSCs both in the pluripotent stage and during early germ layer specification...
May 14, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Stefano Fornasaro, Annalisa Vicario, Luigina De Leo, Alois Bonifacio, Tarcisio Not, Valter Sergo
Raman hyperspectral imaging is an emerging practice in biological and biomedical research for label free analysis of tissues and cells. Using this method, both spatial distribution and spectral information of analyzed samples can be obtained. The current study reports the first Raman microspectroscopic characterisation of colon tissues from patients with Coeliac Disease (CD). The aim was to assess if Raman imaging coupled with hyperspectral multivariate image analysis is capable of detecting the alterations in the biochemical composition of intestinal tissues associated with CD...
May 14, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Emmanuel Luján, Daniela Soto, María S Rosito, Alejandro Soba, Liliana N Guerra, Juan C Calvo, Guillermo Marshall, Cecilia Suárez
Mathematical modelling approaches have become increasingly abundant in cancer research. Tumour infiltration extent and its spatial organization depend both on the tumour type and stage and on the bio-physicochemical characteristics of the microenvironment. This sets a complex scenario that often requires a multidisciplinary and individually adjusted approach. The ultimate goal of this work is to present an experimental/numerical combined method for the development of a three-dimensional mathematical model with the ability to reproduce the growth and infiltration patterns of a given avascular microtumour in response to different microenvironmental conditions...
May 9, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Sreelatha Sarangapani, Ajeetkumar Patil, Yoke Keng Ngeow, Rosmin Elsa Mohan, Anand Asundi, Matthew J Lang
Targeting the oxidative stress response has recently emerged as a promising strategy for the development of therapeutic drugs for a broad spectrum of diseases. Supporting this strategy, we have reported that chitosan nanoparticles synthesized with a controlled size had selective cytotoxicity in leukemia cells through the mechanism related to reactive oxygen species (ROS) generation. Herein, we found that the cellular uptake of chitosan nanoparticles was enhanced in a time dependent manner and inhibited the cellular proliferation of leukemia cells in a dose dependent manner with elevation of the reactive oxygen species (ROS) showing a stronger effect on apoptosis, associated with the upregulation of caspase activity and the depletion of reduced glutathione...
May 3, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Masaya Hagiwara, Rina Nobata, Tomohiro Kawahara
Three-dimensional (3D) cell and tissue cultures more closely mimic biological environments than two-dimensional (2D) cultures and are therefore highly desirable in culture experiments. However, 3D cultures often fail to yield repeatable experimental results because of variation in the initial culture conditions, such as cell density and distribution in the extracellular matrix, and therefore reducing such variation is a paramount concern. Here, we present a 3D culture platform that demonstrates highly repeatable experimental results, obtained by controlling the initial cell cluster shape in the gel cube culture device...
April 24, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Bianca K Stöcker, Johannes Köster, Eli Zamir, Sven Rahmann
Protein interactions are fundamental building blocks of biochemical reaction systems underlying cellular functions. The complexity and functionality of these systems emerge not only from the protein interactions themselves but also from the dependencies between these interactions, as generated by allosteric effects or mutual exclusion due to steric hindrance. Therefore, formal models for integrating and utilizing information about interaction dependencies are of high interest. Here, we describe an approach for endowing protein networks with interaction dependencies using propositional logic, thereby obtaining constrained protein interaction networks ("constrained networks")...
April 20, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
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April 16, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Marie-Elena Brett, Heather E Bomberger, Geneva R Doak, Matthew A Price, James B McCarthy, David K Wood
Numerous studies have demonstrated the importance of altered hyaluronan metabolism to malignant progression of multiple tumor types, including breast carcinomas. Increased hyaluronan (HA) metabolism in the stroma of primary tumors promotes activation of oncogenic signaling pathways that impact tumor initiation, growth, and invasion. Carcinoma cell synthesis and assembly of HA-rich pericellular matrices induces a stromal-independent phenotype, which is associated with cancer progression. Although the pro-tumorigenic role of stromal HA is well established, a novel but unexplored hypothesis is that carcinoma cell-associated HA pericellular matrices promote metastasis of circulating tumor cells...
April 6, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Ding Li, Stacey D Finley
Multiple promoters and inhibitors mediate angiogenesis, the formation of new blood vessels, and these factors represent potential targets for impeding vessel growth in tumors. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor targeted in anti-angiogenic cancer therapies. In addition, thrombospondin-1 (TSP1) is a major endogenous inhibitor of angiogenesis, and TSP1 mimetics are being developed as an alternative type of anti-angiogenic agent. The combination of bevacizumab, an anti-VEGF agent, and ABT-510, a TSP1 mimetic, has been tested in clinical trials to treat advanced solid tumors...
April 6, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Jessica E Kim, Daniel S Reynolds, Muhammad H Zaman, Michael Mak
Cellular processes, such as cell migration, adhesion, and proliferation depend on the interaction between the intracellular environment and the extracellular matrix (ECM). While many studies have explored the role of the microenvironment on cell behavior, the influence of 3D matrix mechanics on intracellular activity is not completely understood. To characterize the relationship between the mechanical components of the microenvironment and intracellular behavior, we use particle-tracking microrheology of metastatic breast cancer cells embedded in 3D collagen gels to quantify the intracellular activity from which the molecular motor activity and stiffness can be determined...
April 5, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Kendra D Nyberg, Samuel L Bruce, Angelyn V Nguyen, Clara K Chan, Navjot K Gill, Tae-Hyung Kim, Erica K Sloan, Amy C Rowat
The physical properties of cells are promising biomarkers for cancer diagnosis and prognosis. Here we determine the physical phenotypes that best distinguish human cancer cell lines, and their relationship to cell invasion. We use the high throughput, single-cell microfluidic method, quantitative deformability cytometry (q-DC), to measure six physical phenotypes including elastic modulus, cell fluidity, transit time, entry time, cell size, and maximum strain at rates of 102 cells per second. By training a k-nearest neighbor machine learning algorithm, we demonstrate that multiparameter analysis of physical phenotypes enhances the accuracy of classifying cancer cell lines compared to single parameters alone...
March 28, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Ning Kang, Quan Guo, Emel Islamzada, Hongshen Ma, Mark D Scott
Despite the critical importance of mechanical (rheological + extrudability) deformability in the vascular flow of lymphocytes, it has been poorly investigated due to the limitations of existing technological tools. Microfluidics analysis of leukocyte deformability offers significant advantages in that it offers high throughput, large sample population and the ability to analyze a heterogeneous population. These advantages are in stark contrast to previous approaches that focused on single cell measurements...
March 23, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Erdem Kucukal, Jane A Little, Umut A Gurkan
Non-adherence and deformability are the key intrinsic biomechanical features of the red blood cell (RBC), which allow it to tightly squeeze and pass through even the narrowest of microcirculatory networks. Blockage of microcirculatory flow, also known as vaso-occlusion, is a consequence of abnormal cellular adhesion to the vascular endothelium. In sickle cell disease (SCD), an inherited anaemia, even though RBCs have been shown to be heterogeneous in adhesiveness and deformability, this has not been studied in the context of physiologically relevant dynamic shear gradients at the microscale...
March 20, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Paola Occhetta, Giuseppe Isu, Marta Lemme, Chiara Conficconi, Philipp Oertle, Christian Räz, Roberta Visone, Giulia Cerino, Marija Plodinec, Marco Rasponi, Anna Marsano
In vitro cardiac models able to mimic the fibrotic process are paramount to develop an effective anti-fibrosis therapy that can regulate fibroblast behaviour upon myocardial injury. In previously developed in vitro models, typical fibrosis features were induced by using scar-like stiffness substrates and/or potent morphogen supplementation in monolayer cultures. In our model, we aimed to mimic in vitro a fibrosis-like environment by applying cyclic stretching of cardiac fibroblasts embedded in three-dimensional fibrin-hydrogels alone...
March 1, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Abdullah A Mosabbir, Anam Qudrat, Kevin Truong
As monoclonal antibodies have two epitopes for their target ligand, they should theoretically dimerize target receptors upon binding. In particular, the dimerization of the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) stimulates early events occurring within minutes (e.g. Ca2+ signal generation) and late events occurring over hours and days (e.g. cell migration in angiogenesis). Although studies have noted that antibodies targeting VEGFR2 (anti-VEGFR2) inhibited cell migration in angiogenesis, we show in this paper that an anti-VEGFR2 stimulus nevertheless triggered a Ca2+ signal in VEGFR2 expressing cells...
March 1, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Natalia Bourguignon, Carolina Attallah, Paola Karp, Ross Booth, Ana Peñaherrera, Cristian Payés, Marcos Oggero, Maximiliano S Pérez, Gustavo Helguera, Betiana Lerner
Herein, a microfluidic device with cistern design for cultivation of adherent eukaryotic cells for the production of recombinant proteins is presented. The geometric configuration of the microchannels in the device provided laminar flow with reduced velocity profiles in the cisterns, resulting in an adequate microenvironment for long-term adherent cell growth with passive pumping flow cycles of 24 hours. CHO-ahIFNα2b and HEK-ahIFNα2b adherent cell lines expressing a novel anti-hIFN-α2b recombinant monoclonal antibody (MAb) for the treatment of systemic lupus erythematosus were cultured on the surface of PDMS/glass microchannels coated with poly-d-lysine...
March 1, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Shuyu Liu, Yan Tan
A novel and label-free, gold nanorods (GNRs)-based resonance light scattering system assay has been developed for the detection of microalgae superoxide dismutase (SOD). The method relies on the fact that interactions between microalgae SOD and GNRs can emit strong fluorescence signals. The prepared GNRs were well dispersed in the solution and intracellular SOD was extracted from Microcystis aeruginosa; the SOD was then absorbed on the surface of the GNRs. The results demonstrated that the intensity of the fluorescence signals increased at 595 nm with an increase in the SOD concentration, the optimum pH value was concluded to be 7...
March 1, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Bianca N Lourenço, Nora L Springer, Daniel Ferreira, Carla Oliveira, Pedro L Granja, Claudia Fischbach
CD44, an abundantly expressed adhesion molecule, and its alternative splice variants have been associated with tumorigenesis and metastasis. In the context of gastric cancer (GC), de novo expression of CD44 variant 6 (CD44v6) is found in more than 60% of GCs, but its role in the pathogenesis and progression of this type of cancer remains unclear. Using a combination of media conditioning experiments and decellularized extracellular matrices (ECMs), this study investigates the hypothesis that CD44v6 overexpression enhances tumor cell malignant behavior by modulating stromal cell-mediated ECM remodeling...
March 1, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
V Onesto, R Narducci, F Amato, L Cancedda, F Gentile
We present a mathematical model that quantifies the amount of information exchanged in bi-dimensional networks of nerve cells as a function of network connectivity Q. Upon varying Q over a significant range, we found that, from a certain cell density onwards, 90% of the maximal information transferred I(Q) in a random neuronal network is already reached with just 40% of the total possible connections Q among the cells. As a consequence, the system would not benefit from additional connections in terms of the amount of I(Q), in agreement with the tendency of brains to minimize Q because of its energetic costs...
February 19, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
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