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      Effect of spectrin network elasticity on the shapes of erythrocyte doublets

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          Abstract

          Red blood cells (RBCs) in plasma or polymer solution interact attractively to form various shapes of RBC doublets. A rich variety of doublet shapes is found, depending on membrane shear and bending elasticity, reduced volumes, and adhesion strength.

          Abstract

          Red blood cell (RBC) aggregates play an important role in determining blood rheology. RBCs in plasma or polymer solution interact attractively to form various shapes of RBC doublets, where the attractive interactions can be varied by changing the solution conditions. A systematic numerical study on RBC doublet formation is performed, which takes into account the shear elasticity of the RBC membrane due to the spectrin cytoskeleton, in addition to the membrane bending rigidity. RBC membranes are modeled by two-dimensional triangular networks of linked vertices, which represent three-dimensional cell shapes. The phase space of RBC doublet shapes in a wide range of adhesion strengths, reduced volumes, and shear elasticities is obtained. The shear elasticity of the RBC membrane changes the doublet phases significantly. Experimental images of RBC doublets in different solutions show similar configurations. Furthermore, we show that rouleau formation is affected by the doublet structure.

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          Most cited references50

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          Configurations of fluid membranes and vesicles

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            The conformation of membranes.

            R Lipowsky (1991)
            Membranes composed of amphiphilic molecules are highly flexible surfaces that determine the architecture of biological systems and provide a basic structural element for complex fluids such as microemulsions. Physical theories have been developed to describe many aspects of their conformational behaviour, such as the preferred shapes and shape transformations of closed vesicles, and the shape fluctuations, random-surface configurations, and adhesion and unbinding of interacting membranes. Understanding of these phenomena has been much improved through fruitful interactions between theory and experiment.
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              Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria.

              We investigate connections between single-cell mechanical properties and subcellular structural reorganization from biochemical factors in the context of two distinctly different human diseases: gastrointestinal tumor and malaria. Although the cell lineages and the biochemical links to pathogenesis are vastly different in these two cases, we compare and contrast chemomechanical pathways whereby intracellular structural rearrangements lead to global changes in mechanical deformability of the cell. This single-cell biomechanical response, in turn, seems to mediate cell mobility and thereby facilitates disease progression in situations where the elastic modulus increases or decreases due to membrane or cytoskeleton reorganization. We first present new experiments on elastic response and energy dissipation under repeated tensile loading of epithelial pancreatic cancer cells in force- or displacement-control. Energy dissipation from repeated stretching significantly increases and the cell's elastic modulus decreases after treatment of Panc-1 pancreatic cancer cells with sphingosylphosphorylcholine (SPC), a bioactive lipid that influences cancer metastasis. When the cell is treated instead with lysophosphatidic acid, which facilitates actin stress fiber formation, neither energy dissipation nor modulus is noticeably affected. Integrating recent studies with our new observations, we ascribe these trends to possible SPC-induced reorganization primarily of keratin network to perinuclear region of cell; the intermediate filament fraction of the cytoskeleton thus appears to dominate deformability of the epithelial cell. Possible consequences of these results to cell mobility and cancer metastasis are postulated. We then turn attention to progressive changes in mechanical properties of the human red blood cell (RBC) infected with the malaria parasite Plasmodium falciparum. We present, for the first time, continuous force-displacement curves obtained from in-vitro deformation of RBC with optical tweezers for different intracellular developmental stages of parasite. The shear modulus of RBC is found to increase up to 10-fold during parasite development, which is a noticeably greater effect than that from prior estimates. By integrating our new experimental results with published literature on deformability of Plasmodium-harbouring RBC, we examine the biochemical conditions mediating increases or decreases in modulus, and their implications for disease progression. Some general perspectives on connections among structure, single-cell mechanical properties and biological responses associated with pathogenic processes are also provided in the context of the two diseases considered in this work.
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                Author and article information

                Journal
                SMOABF
                Soft Matter
                Soft Matter
                Royal Society of Chemistry (RSC)
                1744-683X
                1744-6848
                2018
                2018
                : 14
                : 30
                : 6278-6289
                Affiliations
                [1 ]Theoretical Soft Matter and Biophysics
                [2 ]Institute of Complex Systems and Institute for Advanced Simulation
                [3 ]Forschungszentrum Jülich
                [4 ]52425 Jülich
                [5 ]Germany
                [6 ]Experimental Physics
                [7 ]Saarland University
                [8 ]66123 Saarbrücken
                [9 ]Laboratoire Interdisciplinaire de Physique
                [10 ]CNRS and Université Grenoble Alpes
                [11 ]38402 Saint-Martin d'Hères
                [12 ]France
                [13 ]Physics and Materials Science Research Unit
                Article
                10.1039/C8SM00634B
                30014074
                9ac8d615-e06d-4744-8e8d-146de72900da
                © 2018

                http://rsc.li/journals-terms-of-use

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