1,721,030 research outputs found
Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum
No full textParasitization by malaria-inducing Plasmodium falciparum leads to structural, biochemical, and mechanical modifications to the host red blood cells (RBCs). To study these modifications, we investigate two intrinsic indicators: the refractive index and membrane fluctuations in A falciparum-invaded human RBCs (Pf-RBCs). We report experimental connections between these intrinsic indicators and pathological states. By employing two noninvasive optical techniques, tomographic phase microscopy and diffraction phase microscopy, we extract three-dimensional maps of refractive index and nanoscale cell membrane fluctuations in isolated RBCs. Our systematic experiments cover all intraerythrocytic stages of parasite development under physiological and febrile temperatures. These findings offer potential, and sufficiently general, avenues for identifying, through cell membrane dynamics, pathological states that cause or accompany human diseases.
Lipid bilayer and cytoskeletal interactions in a red blood cell
No full textWe study the biomechanical interactions between the lipid bilayer and the cytoskeleton in a red blood cell (RBC) by developing a general framework for mesoscopic simulations. We treated the lipid bilayer and the cytoskeleton as two distinct components and developed a unique whole-cell model of the RBC, using dissipative particle dynamics (DPD). The model is validated by comparing the predicted results with measurements from four different and independent experiments. First, we simulated the micropipette aspiration and quantified the cytoskeletal deformation. Second, we studied the membrane fluctuations of healthy RBCs and RBCs parasitized to different intraerythrocytic stages by the malaria-inducing parasite Plasmodium falciparum. Third, we subjected the RBC to shear flow and investigated the dependence of its tank-treading frequency on shear rate. Finally, we simulated the bilayer–cytoskeletal detachment in channel flow to quantify the strength of such interactions when the corresponding bonds break. Taken together, these experiments and corresponding systematic DPD simulations probe the governing constitutive response of the cytoskeleton, elastic stiffness, viscous friction, and strength of bilayer–cytoskeletal interactions as well as membrane viscosities. Hence, the DPD simulations and comparisons with available independent experiments serve as validation of the unique two-component model and lead to useful insights into the biomechanical interactions between the lipid bilayer and the cytoskeleton of the RBC. Furthermore, they provide a basis for further studies to probe cell mechanistic processes in health and disease in a manner that guides the design and interpretation of experiments and to develop simulations of phenomena that cannot be studied systematically by experiments alone.National Institutes of Health (U.S.) (Grant R01HL094270)United States. Dept. of Energy (Collaboratory on Mathematics and Mesoscopic Modeling of Materials)Singapore-MIT Alliance for Research and Technology CenterSingapore-MIT Allianc
Quantifying the biophysical characteristics of Plasmodium-falciparum- parasitized red blood cells in microcirculation
No full textThe pathogenicity of Plasmodium falciparum (Pf) malaria results from the stiffening of red blood cells (RBCs) and its ability to adhere to endothelial cells (cytoadherence). The dynamics of Pf-parasitized RBCs is studied by three-dimensional mesoscopic simulations of flow in cylindrical capillaries in order to predict the flow resistance enhancement at different parasitemia levels. In addition, the adhesive dynamics of Pf-RBCs is explored for various parameters revealing several types of cell dynamics such as firm adhesion, very slow slipping along the wall, and intermittent flipping. The parasite inside the RBC is modeled explicitly in order to capture phenomena such as “hindered tumbling” motion of the RBC and the sudden transition from firm RBC cytoadherence to flipping on the endothelial surface. These predictions are in quantitative agreement with recent experimental observations, and thus the three-dimensional modeling method presented here provides new capabilities for guiding and interpreting future in vitro and in vivo studies of malaria.National Institutes of Health (U.S.) (NIH) Grant R01HL094270)National Science Foundation (U.S.) (NSF) Grant CBET-0852948)Singapore-MIT Alliance for Research and Technology (Interdisciplinary Research Group on Infectious Diseases
Multiscale Modeling of Red Blood Cell Mechanics and Blood Flow in Malaria
No full textRed blood cells (RBCs) infected by a Plasmodium parasite in malaria may lose their membrane deformability with a relative membrane stiffening more than ten-fold in comparison with healthy RBCs leading to potential capillary occlusions. Moreover, infected RBCs are able to adhere to other healthy and parasitized cells and to the vascular endothelium resulting in a substantial disruption of normal blood circulation. In the present work, we simulate infected RBCs in malaria using a multiscale RBC model based on the dissipative particle dynamics method, coupling scales at the sub-cellular level with scales at the vessel size. Our objective is to conduct a full validation of the RBC model with a diverse set of experimental data, including temperature dependence, and to identify the limitations of this purely mechanistic model. The simulated elastic deformations of parasitized RBCs match those obtained in optical-tweezers experiments for different stages of intra-erythrocytic parasite development. The rheological properties of RBCs in malaria are compared with those obtained by optical magnetic twisting cytometry and by monitoring membrane fluctuations at room, physiological, and febrile temperatures. We also study the dynamics of infected RBCs in Poiseuille flow in comparison with healthy cells and present validated bulk viscosity predictions of malaria-infected blood for a wide range of parasitemia levels (percentage of infected RBCs with respect to the total number of cells in a unit volume).United States. National Institutes of Health (Grant R01HL094270)National Science Foundation (U.S.). (Grant CBET-0852948)Singapore-MIT Alliance for Research and Technology Cente
Protection mechanisms of the iron-plated armor of a deep sea hydrothermal vent gastropod
No full textBiological exoskeletons, in particular those with unusually robust and multifunctional properties, hold enormous potential for the development of improved load-bearing and protective engineering materials. Here, we report new materials and mechanical design principles of the iron-plated multilayered structure of the natural armor of Crysomallon squamiferum, a recently discovered gastropod mollusc from the Kairei Indian hydrothermal vent field, which is unlike any other known natural or synthetic engineered armor. We have determined through nanoscale experiments and computational simulations of a predatory attack that the specific combination of different materials, microstructures, interfacial geometries, gradation, and layering are advantageous for penetration resistance, energy dissipation, mitigation of fracture and crack arrest, reduction of back deflections, and resistance to bending and tensile loads. The structure-property-performance relationships described are expected to be of technological interest for a variety of civilian and defense applications.National Science Foundation (U.S.)Massachusetts Institute of Technology. Center for Materials Science and Engineering (DMR-0819762)Singapore-MIT Alliance (Advanced Materials for Micro and Nano Systems Programme)Singapore-MIT Alliance (Computational Systems Biology Programme)Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Contract DAAD-19-02-D0002)Raytheon CompanyUnited States. Dept. of Defense ((National Defense Science and Engineering Fellowship (N00244–09–1–0064))Singapore-MIT Alliance for Research and Technology (Interdisciplinary Research Group on Infectious Diseases
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Anisotropic light scattering of individual sickle red blood cells
Get PDFWe present the anisotropic light scattering of individual red blood cells (RBCs) from a patient with sickle cell disease (SCD). To measure light scattering spectra along two independent axes of elongated-shaped sickle RBCs with arbitrary orientation, we introduce the anisotropic Fourier transform light scattering (aFTLS) technique and measured both the static and dynamic anisotropic light scattering. We observed strong anisotropy in light scattering patterns of elongated-shaped sickle RBCs along its major axes using static aFTLS. Dynamic aFTLS analysis reveals the significantly altered biophysical properties in individual sickle RBCs. These results provide evidence that effective viscosity and elasticity of sickle RBCs are significantly different from those of the healthy RBCs.Korea Advanced Institute of Science and Technology (N10110038)Korea Advanced Institute of Science and Technology (N10110048)Korea Advanced Institute of Science and Technology (G04100075)Korea (South). Ministry of Education, Science and Technology (MEST) (Grant number 2009-0087691)National Research Foundation of Korea (NRF-2011-355-c00039)National Institutes of Health (U.S.) (P41-RR02594-18-24)National Institutes of Health (U.S.) (R01HL094270)National Institutes of Health (U.S.) (DK083242
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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