Membrane bilayer balance and erythrocyte shape: a quantitative assessment

Ferrell, James E.; Lee, Kong Joo; Huestis, Wray H.

doi:10.1021/bi00333a006

Cited by 128 publications

(103 citation statements)

References 32 publications

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“…These nonlinearities affect only the details of spicule shape and other highly strained configurations. ‡ ‡ For example, the area difference for the echinocyte III has been estimated to be 1.7 Ϯ 0.6% (9). Note that a single measurement is not really meaningful, because C0 and ⌬A0 enter together into determining ⌬a0.…”

Section: Resultsmentioning

confidence: 99%

Stomatocyte–discocyte–echinocyte sequence of the human red blood cell: Evidence for the bilayer– couple hypothesis from membrane mechanics

Lim

Wortis

Mukhopadhyay

2002

Proc. Natl. Acad. Sci. U.S.A.

442

135

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U nder physiological conditions, a normal human RBC assumes a biconcave discoid (discocyte) shape Ϸ8 m in diameter. It has been known for more than 50 years (1) that a variety of agents can modify this shape systematically and reversibly at constant area and volume § (Fig. 1 Left) (refs. 2 and 3, and ref. 4 and references therein). One set of agents, including anionic amphipaths, high salt, high pH, ATP depletion, cholesterol enrichment, and proximity to a glass surface, induces a series of crenated shapes, called echinocytes, characterized by convex rounded protrusions or spicules. Under further loading, the spicules become smaller and more numerous and eventually (in a process that we shall not discuss further) bud off irreversibly, forming extracellular vesicles composed of plasma membrane materials and leaving behind a more or less spherical body with reduced area and volume (the spheroechinocyte). Another set of agents, including cationic amphipaths, low salt, low pH, and cholesterol depletion, induces concave shapes called stomatocytes. On further loading, multiple concave invaginations are produced, which eventually bud off to form interior vesicles and leave a spherostomatocyte. This ''main sequence'' is universal in the sense that the shapes seen and their order of appearance do not depend on which echinocytogenic or stomatocytogenic agent is used. Other shapes outside of this main sequence are also seen under certain conditions (Fig. 2 Left).The RBC consists of a composite membrane [plasma membrane plus membrane skeleton (MS)] surrounding a fluid interior, so it is natural to search in the membrane properties for an explanation of these shape changes. The first explanation was provided by Sheetz and Singer (5), who proposed that the mechanism involves small changes in the relaxed area difference ⌬A 0 between the two leaflets of the plasma membrane. Thus, any effect that expands the outer leaflet relative to the inner one (increasing ⌬A 0 ) produces a tendency to form convex structures on the cell surface (e.g., echinocytic spicules) to accommodate the extra area; conversely, an expansion of the inner leaflet relative to the outer one (decreasing ⌬A 0 ) favors concavities (e.g., stomatocytic shapes). This so-called bilayer-couple hypothesis explains the universality of the main, stomatocytediscocyte-echinocyte sequence by postulating that all shapechanging agents (chemical, biological, or even physical) act solely or mainly through their effect on ⌬A 0 . Biochemistry comes in only to explain how and to what extent each agent modifies ⌬A 0 . For example, added amphipaths partition differentially between the two bilayer leaflets because of the known asymmetry in composition: The inner leaflet contains a significant fraction of negatively charged lipids (6), thus making it a more attractive environment for cationic amphipaths. Cholesterol, on the other hand, is known to prefer the outer leaflet. Thus, cholesterol addition tends to expand the outer leaflet, whereas addition of cationic amphipaths tends to...

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Section: Resultsmentioning

confidence: 99%

Stomatocyte–discocyte–echinocyte sequence of the human red blood cell: Evidence for the bilayer– couple hypothesis from membrane mechanics

Lim

Wortis

Mukhopadhyay

2002

Proc. Natl. Acad. Sci. U.S.A.

442

135

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“…The FAEE mol % required to alter RBC morphology is unknown, but it may be quite low. Calculations based on molecular dimensions of phospholipids indicate that the differential expansion or contraction of one lipid monolayer by 0.4% to 1.3% of its area is sufficient to produce an abnormal RBC morphology (37). Further investigation is necessary to determine if the observed FAEE changes in RBCs are related to the RBC membrane disorders associated with chronic ethanol ingestion.…”

Section: Resultsmentioning

confidence: 99%

Red blood cell fatty acid ethyl esters: a significant component of fatty acid ethyl esters in the blood

Best

Cluette‐Brown

Teruya

et al. 2003

Journal of Lipid Research

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An association between alcoholism and abnormal red blood cell (RBC) size and shape has long been recognized (1). However, the underlying pathophysiologic mechanisms responsible for the morphologic alterations are incompletely understood (2-6). Fatty acid ethyl esters (FAEEs), esterification products of ethanol and fatty acids, have been shown to be incorporated into phospholipid bilayers up to 30 mol % of total membrane fatty acids (7). FAEEs have been implicated as mediators of ethanolinduced organ damage (8-13) and have clinical utility as markers for ethanol intake (14, 15). Serum and plasma FAEE levels closely correlate with blood ethanol levels, but these circulating FAEEs in blood persist for at least 24 h after ethanol ingestion, long after ethanol is no longer detectable (15, 16).Although the largest reservoir of FAEE synthetic capability appears to reside in the pancreas and the liver (17, 18), enzyme activity that catalyzes FAEE synthesis has been detected in RBCs, white blood cells (WBCs), and platelets. Given the much higher concentration of RBCs in the blood, it has been suggested that RBCs may provide a significant portion of the total FAEE synthase activity in whole blood (19). With this information, the possibility that RBC membranes might synthesize and sequester FAEEs in the blood has been raised.We conducted a controlled clinical trial to determine if FAEEs accumulate and persist within RBCs following ethanol ingestion. The objectives of this study were to determine: 1 ) whether FAEEs appear in RBCs following ethanol ingestion and whether RBC-associated FAEEs correlate with blood ethanol concentration; 2 ) how long FAEEs persist in RBCs after ethanol intake is discontinued; 3 ) whether the fatty acid composition of RBC FAEEs is distinct from the fatty acid composition of FAEEs in plasma; and 4 ) whether RBC and plasma FAEE species undergo a remodeling process with changes in fatty acid composition following discontinuation of ethanol ingestion. METHODSThe study was approved by the institutional review board of the Massachusetts General Hospital. A written informed consent was obtained from each volunteer prior to subject enrollment.Abbreviations: AIC, akaike information criteria; E16:0, ethyl palmitate; E18:0, ethyl stearate; E18:1, ethyl oleate; E18:2, ethyl linoleate; FAEE, fatty acid ethyl ester; GC-MS, gas liquid chromatography-mass spectrometry; RBC, red blood cell; SPE, solid-phase extraction; WBC, white blood cell.

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“…Echinocytes are red blood cells containing spiky plasma membrane protrusions, which form upon addition of phospholipids or other amphipathic molecules to the outer leaflet of plasma membrane (43). Platelets also form similar plasma membrane projections upon activation or addition of phospholipids (44,45). The distinctive morphological changes and inhibition of these changes by addition of apoA-I suggest that they arise from an increased quantity of lipid, probably phospholipid and cholesterol, in the outer leaflet of the plasma membranes.…”

Section: Abc1 Binds To Apoa-i But Not Hdl To Promote Lipid Effluxmentioning

confidence: 98%

Specific Binding of ApoA-I, Enhanced Cholesterol Efflux, and Altered Plasma Membrane Morphology in Cells Expressing ABC1

Wang

Silver

Costet

et al. 2000

Journal of Biological Chemistry

552

463

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Mutations of the ABC1 transporter have been identified as the defect in Tangier disease, characterized by low HDL and cholesterol ester accumulation in macrophages. A full-length mouse ABC1 cDNA was used to investigate the mechanisms of lipid efflux to apoA-I or HDL in transfected 293 cells. ABC1 expression markedly increased cellular cholesterol and phospholipid efflux to apoA-I but had only minor effects on lipid efflux to HDL. The increased lipid efflux appears to involve a direct interaction between apoA-I and ABC1, because ABC1 expression substantially increased apoA-I binding at the cell surface, and chemical cross-linking and immunoprecipitation analysis showed that apoA-I binds directly to ABC1. In contrast to scavenger receptor BI (SR-BI), another cell surface molecule capable of facilitating cholesterol efflux, ABC1 preferentially bound lipid-free apoA-I but not HDL. Immunofluorescence confocal microscopy showed that ABC1 is primarily localized on the cell surface. In the absence of apoA-I, cells overexpressing ABC1 displayed a distinctive morphology, characterized by plasma membrane protrusions and resembling echinocytes that form when there are excess lipids in the outer membrane hemileaflet. The studies provide evidence for a direct interaction between ABC1 and apoA-I, but not HDL, indicating that free apoA-I is the metabolic substrate for ABC1. Plasma membrane ABC1 may act as a phospholipid/cholesterol flippase, providing lipid to bound apoA-I, or to the outer membrane hemileaflet.

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Membrane bilayer balance and erythrocyte shape: a quantitative assessment

Cited by 128 publications

References 32 publications

Stomatocyte–discocyte–echinocyte sequence of the human red blood cell: Evidence for the bilayer– couple hypothesis from membrane mechanics

Stomatocyte–discocyte–echinocyte sequence of the human red blood cell: Evidence for the bilayer– couple hypothesis from membrane mechanics

Red blood cell fatty acid ethyl esters: a significant component of fatty acid ethyl esters in the blood

Specific Binding of ApoA-I, Enhanced Cholesterol Efflux, and Altered Plasma Membrane Morphology in Cells Expressing ABC1

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