1. Cell Physiol Biochem. 2018 Aug 17;48(6):2563-2582. doi: 10.1159/000492700. [Epub 
ahead of print]

Tuning of Differential Lipid Order Between Submicrometric Domains and Surrounding
Membrane Upon Erythrocyte Reshaping.

Leonard C(1)(2), Pollet H(2), Vermylen C(3), Gov N(4), Tyteca D(2),
Mingeot-Leclercq MP(1).

Author information: 
(1)FACM Unit, Louvain Drug Research Institute & Université Catholique de Louvain,
Brussels, Belgium.
(2)CELL Unit, de Duve Institute & Université Catholique de Louvain, Brussels,
(3)PEDI Unit, Institut de Recherche Expérimentale et Clinique & Université
Catholique de Louvain, Brussels, Belgium.
(4)Department of Chemical and Biological Physics, Weizmann Institute of Science, 
Rehovot, Israel.

BACKGROUND/AIMS: Transient nanometric cholesterol- and sphingolipid-enriched
domains, called rafts, are characterized by higher lipid order as compared to
surrounding lipids. Here, we asked whether the seminal concept of highly ordered 
rafts could be refined with the presence of lipid domains exhibiting different
enrichment in cholesterol and sphingomyelin and association with erythrocyte
curvature areas. We also investigated how differences in lipid order between
domains and surrounding membrane (bulk) are regulated and whether changes in
order differences could participate to erythrocyte deformation and vesiculation.
METHODS: We used the fluorescent hydration- and membrane packing-sensitive probe 
Laurdan to determine by imaging mode the Generalized Polarization (GP) values of 
lipid domains vs the surrounding membrane.
RESULTS: Laurdan revealed the majority of sphingomyelin-enriched domains
associated to low erythrocyte curvature areas and part of the
cholesterol-enriched domains associated with high curvature. Both lipid domains
were less ordered than the surrounding lipids in erythrocytes at resting state.
Upon erythrocyte deformation (elliptocytes and stimulation of calcium exchanges) 
or membrane vesiculation (storage at 4°C), lipid domains became more ordered than
the bulk. Upon aging and in membrane fragility diseases (spherocytosis), an
increase in the difference of lipid order between domains and the surrounding
lipids contributed to the initiation of domain vesiculation.
CONCLUSION: The critical role of domain-bulk differential lipid order modulation 
for erythrocyte reshaping is discussed in relation with the pressure exerted by
the cytoskeleton on the membrane.

© 2018 The Author(s). Published by S. Karger AG, Basel.

DOI: 10.1159/000492700 
PMID: 30121671