Phospholipid composition of the mammalian red cell membrane can be rationalized by a superlattice model

Virtanen, Jorma A.; Cheng, Kwan Hon; Somerharju, Pentti

doi:10.1073/pnas.95.9.4964

Cited by 202 publications

(223 citation statements)

References 57 publications

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“…This could demonstrate either a specific requirement for protein-SM interaction in the insertion mechanism or the more general effect the presence of SM has on the dynamics of the membrane. Interestingly, the vesicles composed of 75% PC and 25% SM reflect to some extent the composition of the outer leaflet of the erythrocyte membrane (19). However, as Tir is translocated across the host cell membrane by the TTSS and does not come into contact with the outer leaflet prior to insertion, it is likely that the interaction with these vesicles reflects only the presence of SM.…”

Section: Discussionmentioning

confidence: 99%

“…The final SUV and LUV suspensions were stored at 4°C for 24 h prior to use. The lipid vesicles used in this study were composed of 15% PC, 10% SM, 45% PE, and 30% PS (based on the composition of the human erythrocyte inner leaflet (19), which serves as a mimic of the Tir target membrane in vivo); 100% PC; 75% PC and 25% PE; 75% PC and 25% PS; or 75% PC and 25% SM.…”

Section: Methodsmentioning

confidence: 99%

“…To investigate the mechanism of Tir insertion into the plasma membrane in vivo, we used biophysical and biochemical techniques to probe the protein's interaction with membranes, including a mimic of the human erythrocyte inner leaflet (15% phosphatidylcholine (PC), 10% sphingomyelin (SM), 45% phosphatidylethanolamine (PE), and 30% phosphatidylserine (PS)) (19) as an model of the Tir target membrane and 100% PC as a control model membrane in vitro. These membranes were prepared in the form of small and large unilamellar vesicles, as appropriate.…”

Section: Enteropathogenic Escherichia Coli (Epec)mentioning

confidence: 99%

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Insertion of the Enteropathogenic Escherichia coli Tir Virulence Protein into Membranes in Vitro

Race

Lakey

Banfield

2006

Journal of Biological Chemistry

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Insertion of the enteropathogenic Escherichia coli Tir protein into the plasma membrane of intestinal epithelial cells is a crucial event in infection because it provides a receptor for intimate bacterial adherence. This interaction with the bacterial outer membrane protein intimin is also essential in generating a number of signaling activities associated with virulence. Tir can be modified at various sites by phosphorylation and functionally interacts with multiple host proteins. To investigate the mechanism of membrane insertion and to establish a model system in which the multiple interactions/ functions of Tir can be uncoupled and independently characterized, we used intrinsic tryptophan fluorescence, surface plasmon resonance, and protease digestion assays to show that Tir can insert directly into phospholipid vesicles in a composition-dependent manner to generate the topology reported in vivo. This is the first time that Tir has been shown to insert into membranes in a simple model system in the absence of chemical modification or other factors. These data are consistent with the protein interacting with lipids through two sites. The major site is localized to the transmembrane/intimin-binding domain region and includes Trp 235 , which is shown to be an effective reporter of interaction. The minor site is located within the C-terminal domain. Together, these data support a model in which Tir is released into the cytoplasm by the type III translocon and then independently inserts into the plasma membrane from a cytoplasmic location. A thorough understanding of this mechanism will be crucial to understand the subtleties of enteropathogenic E. coli pathogenesis. Enteropathogenic Escherichia coli (EPEC)3 is a major cause of infantile diarrheal disease in developing countries (1, 2) and is closely related to enterohemorrhagic E. coli (O157), which is an emerging health concern throughout the world (3). EPEC pathogenesis is dependent on (a) an active virulence-associated type III secretion system (TTSS) that directly injects "effector" proteins into host cells and (b) the interaction of Tir (translocated intimin receptor; one such effector protein), inserted into the host cell membrane, with the bacterial outer membrane protein intimin (recently reviewed in Refs. 4 and 5). The intimate adhesion of bacteria to host cell membranes as mediated by the intiminTir interaction is essential for virulence (6 -8) and results in subversion of host cell signaling processes promoting colonization of the intestinal tract (reviewed in Ref. 9).Following delivery by the TTSS, Tir inserts into the host cell plasma membrane, adopting a distinct topology composed of a large extracellular loop (the intimin-binding domain (IBD), residues 255-364) and N-terminal (residues 1-233) and C-terminal (residues 385-550) domains, which remain on the cytosolic face of the membrane (7, 10). These domains are linked by two predicted transmembrane helices (residues 234 -254 and 365-384). In this topology, the extracellular domain is available to ...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Enteropathogenic Escherichia Coli (Epec)mentioning

confidence: 99%

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Insertion of the Enteropathogenic Escherichia coli Tir Virulence Protein into Membranes in Vitro

Race

Lakey

Banfield

2006

Journal of Biological Chemistry

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“…According to this model, amphiphilic phospholipids are arranged in a bilayer structure and proteins are located in or on it. The distribution of these components is asymmetric, that is, negatively charged phospholipids such as phosphatidylserine are predominantly found on the inner, cytoplasmic side of the membrane, whereas neutral, zwitterionic phosphorylcholine lipids such as phosphatidylcholines are more commonly located in the outer leaflet [2]. Phosphatidylcholine provides an inert surface for the biological reactions of proteins and glycoproteins to occur easily on the membrane.…”

Section: Development Of Mpc Polymer Sciencementioning

confidence: 99%

Cell membrane-inspired phospholipid polymers for developing medical devices with excellent biointerfaces

Iwasaki

Ishihara

2012

Science and Technology of Advanced Materials

261

216

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This review article describes fundamental aspects of cell membrane-inspired phospholipid polymers and their usefulness in the development of medical devices. Since the early 1990s, polymers composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) units have been considered in the preparation of biomaterials. MPC polymers can provide an artificial cell membrane structure at the surface and serve as excellent biointerfaces between artificial and biological systems. They have also been applied in the surface modification of some medical devices including long-term implantable artificial organs. An MPC polymer biointerface can suppress unfavorable biological reactions such as protein adsorption and cell adhesion -in other words, specific biomolecules immobilized on an MPC polymer surface retain their original functions. MPC polymers are also being increasingly used for creating biointerfaces with artificial cell membrane structures.

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“…48 The composition of the erythrocyte membrane has been widely studied and its outer leaflet is composed of phospholipids (glycerophospholipids and sphingomyelin), glycosphingolipids (making up the glycocalyx), and cholesterol. 60,61 GMVs were prepared with a composition of 30.5% phosphatidylcholine (DOPC), 27% sphingomyelin (SM), 25% cholesterol, 7% phosphatydilethanolamine (DOPE), and 10% ganglioside GM1, mimicking the outer leaflet of the RBC membrane [60][61][62] (Fig. 5a).…”

Section: †)mentioning

confidence: 99%

Influence of the glycocalyx and plasma membrane composition on amphiphilic gold nanoparticle association with erythrocytes

Atukorale

Bekdemir

et al. 2015

Nanoscale

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Erythrocytes are attractive as potential cell-based drug carriers because of their abundance and long lifespan in vivo. Existing methods for loading drug cargos into erythrocytes include hypotonic treatments, electroporation, and covalent attachment onto the membrane, all of which require ex vivo manipulation.Here, we characterized the properties of amphiphilic gold nanoparticles (amph-AuNPs), comprised of a ∼2.3 nm gold core and an amphiphilic ligand shell, which are able to embed spontaneously within erythrocyte membranes and might provide a means to load drugs into red blood cells (RBCs) directly in vivo. Particle interaction with RBC membranes occurred rapidly at physiological temperature. We further show that amph-AuNP uptake by RBCs was limited by the glycocalyx and was particularly influenced by sialic acids on cell surface proteoglycans. Using a reductionist model membrane system with synthetic lipid vesicles, we confirmed the importance of membrane fluidity and the glycocalyx in regulating amph-AuNP/ membrane interactions. These results thus provide evidence for the interaction of amph-AuNPs with erythrocyte membranes and identify key membrane components that govern this interaction, providing a framework for the development of amph-AuNP-carrying erythrocyte 'pharmacytes' in vivo.

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Phospholipid composition of the mammalian red cell membrane can be rationalized by a superlattice model

Cited by 202 publications

References 57 publications

Insertion of the Enteropathogenic Escherichia coli Tir Virulence Protein into Membranes in Vitro

Insertion of the Enteropathogenic Escherichia coli Tir Virulence Protein into Membranes in Vitro

Cell membrane-inspired phospholipid polymers for developing medical devices with excellent biointerfaces

Influence of the glycocalyx and plasma membrane composition on amphiphilic gold nanoparticle association with erythrocytes

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