{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:45:28Z","timestamp":1773391528666,"version":"3.50.1"},"reference-count":59,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Red blood cell (RBC) deformability is altered in inherited RBC disorders but the mechanism behind this is poorly understood. Here, we explored the molecular, biophysical, morphological, and functional consequences of \u03b1-spectrin mutations in a patient with hereditary elliptocytosis (pEl) almost exclusively expressing the Pro260 variant of SPTA1 and her mother (pElm), heterozygous for this mutation. At the molecular level, the pEI RBC proteome was globally preserved but spectrin density at cell edges was increased. Decreased phosphatidylserine vs. increased lysophosphatidylserine species, and enhanced lipid peroxidation, methemoglobin, and plasma acid sphingomyelinase (aSMase) activity were observed. At the biophysical level, although membrane transversal asymmetry was preserved, curvature at RBC edges and rigidity were increased. Lipid domains were altered for membrane:cytoskeleton anchorage, cholesterol content and response to Ca2+ exchange stimulation. At the morphological and functional levels, pEl RBCs exhibited reduced size and circularity, increased fragility and impaired membrane Ca2+ exchanges. The contribution of increased membrane curvature to the pEl phenotype was shown by mechanistic experiments in healthy RBCs upon lysophosphatidylserine membrane insertion. The role of lipid domain defects was proved by cholesterol depletion and aSMase inhibition in pEl. The data indicate that aberrant membrane content and biophysical properties alter pEl RBC morphology and functionality.<\/jats:p>","DOI":"10.3390\/biom10081120","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T03:36:38Z","timestamp":1596080198000},"page":"1120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Aberrant Membrane Composition and Biophysical Properties Impair Erythrocyte Morphology and Functionality in Elliptocytosis"],"prefix":"10.3390","volume":"10","author":[{"given":"H\u00e9l\u00e8ne","family":"Pollet","sequence":"first","affiliation":[{"name":"CELL Unit &amp; PICT Imaging Platform, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne-Sophie","family":"Cloos","sequence":"additional","affiliation":[{"name":"CELL Unit &amp; PICT Imaging Platform, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amaury","family":"Stommen","sequence":"additional","affiliation":[{"name":"CELL Unit &amp; PICT Imaging Platform, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliette","family":"Vanderroost","sequence":"additional","affiliation":[{"name":"CELL Unit &amp; PICT Imaging Platform, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Conrard","sequence":"additional","affiliation":[{"name":"CELL Unit &amp; PICT Imaging Platform, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4784-3510","authenticated-orcid":false,"given":"Adrien","family":"Paquot","sequence":"additional","affiliation":[{"name":"Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marine","family":"Ghodsi","sequence":"additional","affiliation":[{"name":"CELL Unit &amp; PICT Imaging Platform, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e9lanie","family":"Carquin","sequence":"additional","affiliation":[{"name":"CELL Unit &amp; PICT Imaging Platform, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"L\u00e9onard","sequence":"additional","affiliation":[{"name":"CELL Unit &amp; PICT Imaging Platform, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Guthmann","sequence":"additional","affiliation":[{"name":"CELL Unit &amp; PICT Imaging Platform, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxime","family":"Lingurski","sequence":"additional","affiliation":[{"name":"CELL Unit &amp; PICT Imaging Platform, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiane","family":"Vermylen","sequence":"additional","affiliation":[{"name":"PEDI Unit, Institut de Recherche Exp\u00e9rimentale et Clinique &amp; Saint-Luc Hospital, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7510-175X","authenticated-orcid":false,"given":"Theodore","family":"Killian","sequence":"additional","affiliation":[{"name":"Computational Biology and Bioinformatics Unit, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1520-2268","authenticated-orcid":false,"given":"Laurent","family":"Gatto","sequence":"additional","affiliation":[{"name":"Computational Biology and Bioinformatics Unit, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Rider","sequence":"additional","affiliation":[{"name":"PHOS Unit &amp; MASSPROT Proteomics Platform, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5449-1541","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Pyr dit Ruys","sequence":"additional","affiliation":[{"name":"PHOS Unit &amp; MASSPROT Proteomics Platform, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7648-8282","authenticated-orcid":false,"given":"Didier","family":"Vertommen","sequence":"additional","affiliation":[{"name":"PHOS Unit &amp; MASSPROT Proteomics Platform, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6236-338X","authenticated-orcid":false,"given":"Miikka","family":"Vikkula","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"},{"name":"Walloon Excellence in Life Sciences and Biotechnology (WELBIO), de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9548-8229","authenticated-orcid":false,"given":"Pascal","family":"Brouillard","sequence":"additional","affiliation":[{"name":"Human Molecular Genetics, de Duve Institute, UCLouvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Van Der Smissen","sequence":"additional","affiliation":[{"name":"CELL Unit &amp; 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