Contribution of plasma membrane lipid domains to red blood cell (re)shaping

Léonard, Catherine; Conrard, Louise; Guthmann, M.; Pollet, Hélène; Carquin, Mélanie; Vermylen, Christiane; Gailly, P.; Smissen, Patrick Van Der; Mingeot-Leclercq, M. P.; Tyteca, Donatienne

doi:10.1038/s41598-017-04388-z

Cited by 40 publications

(90 citation statements)

References 45 publications

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“…Regarding lipid domain contribution to RBC reshaping, we have previously shown that the first population of domains, i.e. those mostly enriched in chol, gather in increased curvature areas upon RBC deformation [29]. Here, we provide experimental evidence for the differential contribution of the two other populations of lipid domains in RBC calcium exchanges.…”

Section: Introductionmentioning

confidence: 51%

“…2A). This technique allowed to observe alternating regions of high curvature (HC) at the edges of the RBCs and of low curvature (LC) at the center of the cell [29]. We showed that PC-and GM1-enriched domains were preferentially associated with the LC areas of the RBC, like SM-enriched domains (green, blue and orange arrowheads, Fig.…”

Section: Statistical Analysesmentioning

confidence: 92%

“…1A and quantification in Fig. 1C), those enriched in PC and GM1 seemed restricted to the central area of spread RBC membrane (defined as in [29]). …”

Section: Statistical Analysesmentioning

confidence: 99%

“…Statistical significance was tested either with two-sample t-test or one-way ANOVA followed by Tukey's post-hoc test (NS, not significant; * p < 0.05; ** p < 0.01 and *** p < 0.001). [25,26] and preferentially associate with high and low curvature areas of the biconcave RBC membrane [29]. This analysis was limited to chol and SM while not considering PC, another abundant class of outer PM leaflet lipids, or glycosphingolipids, known to play key pathophysiological roles.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…lipid order and association with membrane curvature areas) and differentially contribute to the RBC deformation. For instance, chol-enriched domains gather in high-curvature membrane areas under RBC stretching and might thus increase deformability and membrane resistance under deformation; while SM-enriched domains, which increase in abundance after deformation, could be linked to RBC shape restoration after deformation [29].…”

Section: Introductionmentioning

confidence: 99%

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Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Conrard

Stommen

Cloos

et al. 2018

Cell Physiol Biochem

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Background/Aims: Red blood cells (RBC) have been shown to exhibit stable submicrometric lipid domains enriched in cholesterol (chol), sphingomyelin (SM), phosphatidylcholine (PC) or ganglioside GM1, which represent the four main lipid classes of their outer plasma membrane leaflet. However, whether those lipid domains co-exist at the RBC surface or are spatially related and whether and how they are subjected to reorganization upon RBC deformation are not known. Methods: Using fluorescence and/or confocal microscopy and well-validated probes, we compared these four lipid-enriched domains for their abundance, curvature association, lipid order, temperature dependence, spatial dissociation and sensitivity to RBC mechanical stimulation. Results: Our data suggest that three populations of lipid domains with decreasing abundance coexist at the RBC surface: (i) chol-enriched ones, associated with RBC high curvature areas; (ii) GM1/PC/chol-enriched ones, present in low curvature areas; and (iii) SM/PC/chol-enriched ones, also found in low curvature areas. Whereas chol-enriched domains gather in increased curvature areas upon RBC deformation, low curvature-associated lipid domains increase in abundance either upon calcium influx during RBC deformation (GM1/PC/chol-enriched domains) or upon secondary calcium efflux during RBC shape restoration (SM/PC/chol-enriched domains). Hence, abrogation of these two domain populations is accompanied by a strong impairment of the intracellular calcium balance. Conclusion: Lipid domains could contribute to calcium influx and efflux by controlling the membrane distribution and/or the activity of the mechano-activated ion channel Piezo1 and the calcium pump PMCA. Whether this results from lipid domain biophysical properties, the strength of their anchorage to the underlying cytoskeleton and/or their correspondence with inner plasma membrane leaflet lipids remains to be demonstrated.

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Section: Introductionmentioning

confidence: 51%

Section: Statistical Analysesmentioning

confidence: 92%

“…1A and quantification in Fig. 1C), those enriched in PC and GM1 seemed restricted to the central area of spread RBC membrane (defined as in [29]). …”

Section: Statistical Analysesmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Conrard

Stommen

Cloos

et al. 2018

Cell Physiol Biochem

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Engineering Synthetic Erythrocytes as Next‐Generation Blood Substitutes

Gomes,

Jeong,

Shin

et al. 2024

Adv Funct Materials

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Blood scarcity is one of the main causes of healthcare disruptions worldwide, with blood shortages occurring at an alarming rate. Over the last decades, blood substitutes have aimed at reinforcing the supply of blood, with several products (e.g., hemoglobin (Hb)‐based oxygen (O2) carriers, perfluorocarbons (PFC)) achieving a limited degree of success. Regardless, there is still no widespread solution to this problem due to persistent challenges in product safety and scalability. In this Review, different advances are described in the field of blood substitution, particularly in the development of artificial red blood cells, otherwise known as engineered erythrocytes (EE). The different strategies are categorized into natural, synthetic, or hybrid approaches, and discuss their potential in terms of safety and scalability. Synthetic EEs are identified as the most powerful approach, and describe erythrocytes from a materials engineering perspective. Their biological structure and function are reviewed, as well as explore different methods of assembling a material‐based cell. Specifically, it is discussed how to recreate size, shape, and deformability through particle fabrication, and how to recreate the functional machinery through synthetic biology and nanotechnology. It is concluded by describing the versatile nature of synthetic erythrocytes in medicine and pharmaceuticals and propose specific directions for the field of erythrocyte engineering.

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A novel missense variant in ATP11C is associated with reduced red blood cell phosphatidylserine flippase activity and mild hereditary hemolytic anemia

van Dijk,

van Oirschot,

Harrison

et al. 2023

American J Hematol

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Adenosine Triphosphatase (ATPase) Phospholipid Transporting 11C gene (ATP11C) encodes the major phosphatidylserine (PS) flippase in human red blood cells (RBCs). Flippases actively transport phospholipids (e.g., PS) from the outer to the inner leaflet to establish and maintain phospholipid asymmetry of the lipid bilayer of cell membranes. This asymmetry is crucial for survival since externalized PS triggers phagocytosis by splenic macrophages. Here we report on pathophysiological consequences of decreased flippase activity, prompted by a patient with hemolytic anemia and hemizygosity for a novel c.2365C > T p.(Leu789Phe) missense variant in ATP11C. ATP11C protein expression was strongly reduced by 58% in patient‐derived RBC ghosts. Furthermore, functional characterization showed only 26% PS flippase activity. These results were confirmed by recombinant mutant ATP11C protein expression in HEK293T cells, which was decreased to 27% compared to wild type, whereas PS‐stimulated ATPase activity was decreased by 57%. Patient RBCs showed a mild increase in PS surface exposure when compared to control RBCs, which further increased in the most dense RBCs after RBC storage stress. The increase in PS was not due to higher global membrane content of PS or other phospholipids. In contrast, membrane lipid lateral distribution showed increased abundance of cholesterol‐enriched domains in RBC low curvature areas. Finally, more dense RBCs and subtle changes in RBC morphology under flow hint toward alterations in flow behavior of ATP11C‐deficient RBCs. Altogether, ATP11C deficiency is the likely cause of hemolytic anemia in our patient, thereby underlining the physiological role and relevance of this flippase in human RBCs.

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Contribution of plasma membrane lipid domains to red blood cell (re)shaping

Cited by 40 publications

References 45 publications

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Engineering Synthetic Erythrocytes as Next‐Generation Blood Substitutes

A novel missense variant in ATP11C is associated with reduced red blood cell phosphatidylserine flippase activity and mild hereditary hemolytic anemia

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