Impaired Cytoskeletal and Membrane Biophysical Properties of Acanthocytes in Hypobetalipoproteinemia – A Case Study

• DOI: 10.3389/fphys.2021.638027
• Publication Date: 2021-02-23T05:05:54Z
• Authors: Anne-Sophie Cloos; Laura G. M. Daenen; Mauriane Maja; Amaury Stommen; Juliette Vanderroost; Patrick Van Der S...; Minke Rab; Jan Westerink; Eric Mignolet; Yvan Larondelle; Romano Terrasi; Giulio G. Muccioli; Andra C. Dumitru; David Alsteens; Richard van Wijk; Donatienne Tyteca
• Keywords: Echinocyte; Erythrocyte fragility; Membrane Curvature

Familial hypobetalipoproteinemia is a metabolic disorder mainly caused by mutations in the apolipoprotein B gene. In its homozygous form it can lead without treatment to severe ophthalmological and neurological manifestations. contrast, heterozygous generally asymptomatic but associated with low risk of cardiovascular disease. Acanthocytes or thorny red blood cells (RBCs) are described for both forms However, those morphological changes poorly characterized their potential consequences RBC functionality not understood. Thus, present study, we asked whether, what extent how acanthocytes from patient familial could exhibit altered functionality. represented 50% total population contained mitoTracker-positive surface patches, indicating presence mitochondrial fragments. While osmotic fragility, calcium content ATP homeostasis were preserved, slight decrease deformability combined an increase intracellular free reactive oxygen species observed. The spectrin cytoskeleton was altered, showing lower density enrichment patches. At membrane level, no obvious modification fatty acids nor cholesterol detected ceramide all increased. Membrane stiffness curvature also increased whereas transversal asymmetry preserved. lateral highly impaired showing: (i) abundance decreased sphingomyelin-enriched domains; (ii) spicules; (iii) We propose that oxidative stress induces cytoskeletal alterations, leading lipid distribution domains spicules. addition, ceramide- spectrin-enriched patches result maturation defect. Altogether, data indicate while only mildly impaired. might affect precursors disturbed maturation. This study paves way use biophysics vital imaging as new methods diagnosis disorders.