Nanoscale adhesion profiling and membrane characterisation in sickle cell disease using hybrid atomic force microscopy-IR spectroscopy.

Autor: Fellows AP; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Casford MTL; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK., Davies PB; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. Electronic address: pbd2@cam.ac.uk., Gibson JS; Department of Veterinary Medicine, Madingley Road, Cambridge, CB3 0ES, UK. Electronic address: jsg1001@cam.ac.uk., Brewin JN; Department of Paediatric Haematology, King's College Hospital, London, SE5 9RS, UK., Rees DC; Department of Paediatric Haematology, King's College Hospital, London, SE5 9RS, UK.
Jazyk: angličtina
Zdroj: Colloids and surfaces. B, Biointerfaces [Colloids Surf B Biointerfaces] 2021 Jan; Vol. 197, pp. 111383. Date of Electronic Publication: 2020 Oct 03.
DOI: 10.1016/j.colsurfb.2020.111383
Abstrakt: Sickle cell disease (SCD) presents a significant global health problem. At present there is no effective treatment, with most being supportive for its associated complications such as the vaso-occlusive crises that result from increased cell adhesion. Hypoxic sickle cells have previously shown greater phosphatidylserine (PS) exposure and oxidative damage, as well as being notably "stickier" suggesting that increased cell cohesion and adhesion to the blood vessel endothelium is a possible mechanism for vaso-occlusion. The present work uses the hybrid technique of atomic force microscopy nano-infrared spectroscopy (AFM-IR) to probe changes to the coefficient of friction and C-O IR intensity in SCD on a nanoscale for dried red blood cells (RBCs) fixed under conditions of hypoxia and correlates these observations with adhesive interactions at the membrane. Using functionalised AFM tips, it has been possible to probe adhesive interactions between hydrophilic and hydrophobic moieties exposed at the surface of the dried RBCs fixed under different oxygenation states and for different cell genotypes. The results are consistent with greater PS-exposure and oxidative damage in hypoxic sickle cells, as previously proposed, and also show strong correlation between localised oxidative damage and increased adhesion. A mechanistic explanation involving significant lipid tail disruption as a result of oxidative action, in combination with differing concentrations of externalised PS lipids, is proposed to explain the observed adhesion behaviour of each type of cell.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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