title: Single-cell evaluation of red blood cell bio-mechanical and nano-structural alterations upon chemically induced oxidative stress.
abstract: Erythroid cells, specifically red blood cells (RBCs), are constantly exposed to highly reactive radicals during cellular gaseous exchange. Such exposure often exceeds the cells' innate anti-oxidant defense systems, leading to progressive damage and eventual senescence. One of the contributing factors to this process are alterations to hemoglobin conformation and globin binding to red cell cytoskeleton. However, in addition to the aforementioned changes, it is possible that oxidative damage induces critical changes to the erythrocyte cytoskeleton and corresponding bio-mechanical and nano-structural properties of the red cell membrane. To quantitatively characterize how oxidative damage accounts for such changes, we employed single-cell manipulation techniques such as micropipette aspiration and atomic force microscopy (AFM) on RBCs. These investigations demonstrated visible morphological changes upon chemically induced oxidative damage (using hydrogen peroxide, diamide, primaquine bisphosphate and cumene hydroperoxide). Our results provide previously unavailable observations on remarkable changes in red cell cytoskeletal architecture and membrane stiffness due to oxidative damage. Furthermore, we also demonstrate that a pathogen that infects human blood cells, Plasmodium falciparum was unable to penetrate through the oxidant-exposed RBCs that have damaged cytoskeleton and stiffer membranes. This indicates the importance of bio-physical factors pertinent to aged RBCs and it's relevance to malaria infectivity.
authors.affiliation: 1] Engineering Product Development (EPD) Pillar, Singapore University of Technology &Design (SUTD), Singapore [2] Interdisciplinary Research Group of Infectious Diseases, Singapore MIT Alliance for Research &Technology Centre (SMART), Singapore.
authors.forename: Ameya
authors.initials: A
authors.lastname: Sinha
authors.affiliation: Engineering Product Development (EPD) Pillar, Singapore University of Technology &Design (SUTD), Singapore.
authors.forename: Trang T T
authors.initials: TT
authors.lastname: Chu
authors.affiliation: 1] Interdisciplinary Research Group of Infectious Diseases, Singapore MIT Alliance for Research &Technology Centre (SMART), Singapore [2] Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge-Massachusetts, U.S.A.
authors.forename: Ming
authors.initials: M
authors.lastname: Dao
authors.affiliation: Engineering Product Development (EPD) Pillar, Singapore University of Technology &Design (SUTD), Singapore.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Chandramohanadas
mesh_terms: D004907:Erythrocyte Deformability; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010961:Plasmodium / Q000502:physiology; D059010:Single-Cell Analysis / Q000379:methods
chemical_list: D016877:Oxidants