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Cyclic Mechanical Stresses Alter Erythrocyte Membrane Composition and Microstructure and Trigger Macrophage Phagocytosis.

ABSTRACT: Red blood cells (RBCs) are cleared from the circulation when they become damaged or display aging signals targeted by macrophages. This process occurs mainly in the spleen, where blood flows through submicrometric constrictions called inter-endothelial slits (IES), subjecting RBCs to large-amplitude deformations. In this work, RBCs are circulated through microfluidic devices containing microchannels that replicate the IES. The cyclic mechanical stresses experienced by the cells affect their biophysical properties and molecular composition, accelerating cell aging. Specifically, RBCs quickly transition to a more spherical, less deformable phenotype that hinders microchannel passage, causing hemolysis. This transition is associated with the release of membrane vesicles, which self-extinguishes as the spacing between membrane-cytoskeleton linkers becomes tighter. Proteomics analysis of the mechanically aged RBCs reveals significant losses of essential proteins involved in antioxidant protection, gas transport, and cell metabolism. Finally, it is shown that these changes make mechanically aged RBCs more susceptible to macrophage phagocytosis. These results provide a comprehensive model explaining how physical stress induces RBC clearance in the spleen. The data also suggest new biomarkers of early "hemodamage" and inflammation preceding hemolysis in RBCs subjected to mechanical stress.

SUBMITTER: Garcia-Herreros A

PROVIDER: S-EPMC9284186 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:It is known that the yttria-stabilized zirconia (YSZ) material has superior thermal, mechanical, and electrical properties. This material is used for manufacturing products and components of air heaters, hydrogen reformers, cracking furnaces, fired heaters, etc. This work is aimed at searching for the optimal sintering mode of YSZ ceramics that provides a high crack growth resistance. Beam specimens of ZrO2 ceramics doped with 6, 7, and 8 mol% Y2O3 (hereinafter: 6YSZ, 7YSZ, and 8YSZ) were prepared using a conventional sintering technique. Four sintering temperatures (1450 °C, 1500 °C, 1550 °C, and 1600 °C) were used for the 6YSZ series and two sintering temperatures (1550 °C and 1600 °C) were used for the 7YSZ and 8YSZ series. The series of sintered specimens were ground and polished to reach a good surface quality. Several mechanical tests of the materials were performed, namely, the microhardness test, fracture toughness test by the indentation method, and single-edge notch beam (SENB) test under three-point bending. Based on XRD analysis, the phase balance (percentages of tetragonal, cubic, and monoclinic ZrO2 phases) of each composition was substantiated. The morphology of the fracture surfaces of specimens after both the fracture toughness tests was studied in relation to the mechanical behavior of the specimens and the microstructure of corresponding materials. SEM-EDX analysis was used for microstructural characterization. It was found that both the yttria percentage and sintering temperature affect the mechanical behavior of the ceramics. Optimal chemical composition and sintering temperature were determined for the studied series of ceramics. The maximum transformation toughening effect was revealed for ZrO2-6 mol% Y2O3 ceramics during indentation. However, in the case of a SENB test, the maximum transformation toughening effect in the crack tip vicinity was found in ZrO2-7 mol% Y2O3 ceramics. The conditions for obtaining YSZ ceramics with high fracture toughness are discussed.

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Cyclic Mechanical Stresses Alter Erythrocyte Membrane Composition and Microstructure and Trigger Macrophage Phagocytosis.

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