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#phospholipid

6 public questions tagged with this topic.

Plasma Membrane

Which of the following is true for phosphatidylcholine?

Phosphatidylcholine dominates eukaryotic membranes, constituting 40-50% of total phospholipid, existing as zwitterion at neutral pH with positively charged trimethylammonium and negatively charged phosphate, yielding net neutral molecule that stabilizes lamellar bilayer phase and prevents excessive electrostatic repulsion between headgroups. Its cylindrical molecular geometry with roughly equal cross-section of headgroup and two acyl chains favors planar bilayer formation, contrasting cone-shaped PE that induces curvature. Physiologically outstanding example is lung surfactant synthesized by type II alveolar cells in lamellar bodies containing dipalmitoylphosphatidylcholine DPPC with two saturated palmitate chains plus surfactant proteins SP-B and SP-C; DPPC reduces alveolar surface tension to near zero at end-expiration, preventing alveolar collapse and decreasing work of breathing. Premature infants deficient in surfactant develop respiratory distress syndrome treated with exogenous surfactant replacement therapy. In plasma membrane outer leaflet, PC serves as reservoir for signaling lipid phosphatidic acid via phospholipase D and as substrate for sphingomyelin synthesis, illustrating structural and metabolic versatility beyond membrane structure.

Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 10: Phosphatidylcholine and Pulmonary Surfactant.

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Properties of Plasma Membrane

Which phospholipid is associated with apoptosis when it flips to the outer leaflet?

Phosphatidylserine externalization is tightly regulated apoptotic signature converting silent inner lipid into eat me signal for phagocytes and coagulation cofactor. In viable cells phosphatidylserine restricted inside by flippase ATP11C ATP11A requiring CDC50A chaperone maintaining aminophospholipid gradient preventing thrombin generation and immune recognition. Apoptotic executioner caspases three and seven cleave ATP11C at conserved DEVD site inactivating inward pumping and cleave Xkr8 at C terminus unmasking scramblase activity requiring binding to basigin neuroplastin heterodimer. External PS binds Annexin V calcium dependent manner enabling flow cytometric detection of apoptosis, bridges MFG E8 to integrin alphaVbeta3, engages Tim4 stabilin two and BAI1 receptors initiating engulfment without inflammation. Procoagulant platelets also expose PS via TMEM16F providing scaffold for factors Va Xa tenase prothrombinase amplifying clot formation. Other lipids PC SM remain outside constitutively without signaling role. Mutations causing Scott syndrome impair TMEM16F leading to bleeding diathesis linking lipid topology to immunity hemostasis and therapeutic annexin imaging applications.

Ref: Nagata et al., Cell Death & Differentiation 2016, PS exposure via flippase scramblase in apoptosis and coagulation.

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Properties of Plasma Membrane

Which phospholipid is found in both leaflets but varies in abundance?

Phospholipid asymmetry is not absolute exclusion but quantitative enrichment regulated by energy dependent translocators. Phosphatidylcholine illustrates this because it is detected in both exoplasmic and cytoplasmic leaflets, yet outer leaflet holds roughly sixty percent more than inner, unlike phosphatidylserine strongly restricted inside. Synthesis occurs in endoplasmic reticulum via Kennedy pathway choline phosphotransferase CPT, then delivery to plasma membrane and sorting by P4 ATPase flippases ATP11C complexed with CDC50A that internalize aminophospholipids and ABC floppases ABCA1 ABCB4 that externalize choline lipids, while calcium dependent scramblases TMEM16F and Xkr8 collapse gradients during platelet activation and apoptosis. PC's cylindrical geometry with bulky quaternary amine head stabilizes lamellar phase, and variable acyl unsaturation tunes fluidity and thickness locally. Classical experiments using trinitrobenzenesulfonate labeling, phospholipase A2 hydrolysis, and NBD analog back extraction confirmed PC in both sides. Graded distribution influences spontaneous curvature, protein insertion, and budding vesicles, concept essential for drug permeability and membrane topology in NEET, CSIR NET, and GATE examinations.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 10: Membrane lipid asymmetry and translocators.

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Properties of Plasma Membrane

What is the key difference between bilayers and liposomes?

Distinction between bilayer organization and vesicular structures illustrates supramolecular assembly hierarchy. Phospholipid bilayer fundamental two-dimensional fluid with two opposed leaflets hydrophobic tails interior hydrocarbon slab three to four nanometer low dielectric excluding water, hydrophilic headgroups hydrated outward facing aqueous phases intra and extracellular, forms flexible sheet capable of undulations bending modulus about ten to twenty kBT, can exist as planar black lipid membrane across aperture separating two aqueous compartments or supported bilayer on mica for AFM. Liposome synthetic spherical vesicle composed of one or more concentric closed bilayers each enclosing discrete aqueous compartment distinct internal volume chemically isolated from bulk external medium, generated by hydrating dried lipid film mechanical agitation ultrasound extrusion hundred nanometer filter or detergent removal methods. Classification small unilamellar thirty to fifty nanometers, large unilamellar hundred to thousand nanometers, multilamellar onion-like many lamellae. Applications drug delivery doxorubicin liposomal, gene delivery, membrane protein reconstitution functional assays, permeability studies, vaccine adjuvants. Key difference therefore liposomes enclose aqueous core while planar bilayer sheet does not although both share bilayer building block.

Ref: Bangham et al., Liposomes as Models of Biological Membranes, J Mol Biol 1965.

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Properties of Plasma Membrane

Which phospholipid is predominantly found in the inner leaflet of the plasma membrane?

Distribution of phosphatidylserine asymmetry extensively studied using chemical probes and protein ligands. In resting healthy mammalian cells phosphatidylserine comprises ten to fifteen percent total phospholipid localized predominantly inner leaflet due to active inward transport by flippase P4-ATPase ATP11C and ATP8A1 maintaining steep gradient outer less than two percent. Inner PS negative charge facilitates recruitment of proteins with polybasic motifs K-Ras C-terminal lysine stretch c-Src and protein kinase C C2 domain calcium dependent binding promoting signal transduction at membrane. PS also cofactor for protein kinase C activation and factor Xa prothrombinase assembly requires outer exposure. During apoptosis executioner caspase cleavage inactivates flippase and activates scramblase TMEM16F and Xkr8 causing rapid externalization of PS within minutes recognized by macrophage receptors TIM4 TAM family bridging via Gas6 protein S triggering engulfment anti-inflammatory response and blood coagulation cascade amplification via factor V Va binding to exposed PS supporting thrombin generation. Phosphatidylcholine sphingomyelin dominate outer leaflet providing neutral zwitterionic surface. Inner enrichment therefore hallmark functional asymmetry.

Ref: Leventis and Grinstein, Phosphatidylserine Distribution and Flippase, Annu Rev Biophys 2010.

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