Plasma Membrane

Plasma Membrane

Which lipid is unique to mitochondria?

Cardiolipin, diphosphatidylglycerol, uniquely contains two phosphatidic acid moieties linked by central glycerol bridge, resulting in four acyl chains, typically tetralinoleoyl 18:2 in cardiac tissue conferring fluidity, and small headgroup with two negative charges at physiological pH. Synthesized in mitochondria by condensation of phosphatidylglycerol and CDP-diacylglycerol catalyzed by cardiolipin synthase CRLS1 on matrix side of inner membrane followed by remodeling via tafazzin transacylase exchanging chains to mature unsaturated form. Its conical shape with large hydrophobic volume imposes negative curvature crucial for tight folds of cristae membranes, while anionic headgroup binds to respiratory supercomplexes I/III2/IV, ADP/ATP carrier AAC, phosphate carrier, and Complex V dimerization interface stabilizing oxidative phosphorylation efficiency and reducing electron leak and reactive oxygen species. During apoptosis and mitophagy, oxidized cardiolipin translocates to outer membrane where it interacts with LC3 autophagy protein and cytochrome c release machinery triggering cell death. Barth syndrome due to TAZ mutation demonstrates cardiomyopathy from defective remodeling, highlighting organelle-specific requirement absent from plasma membrane.

Ref: Lehninger Principles of Biochemistry, 8th ed., Chapter 19: Cardiolipin, Mitochondrial Signature Lipid.

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Plasma Membrane

Which of the following influences membrane curvature?

Intrinsic lipid shape contributes substantially to membrane bending energy as described by Helfrich elastic theory and packing parameter concepts. Phospholipids with small headgroup relative to bulky unsaturated tail volume possess negative intrinsic curvature favoring concave bending of monolayer. Phosphatidylethanolamine possesses ethanolamine headgroup substantially smaller than choline of phosphatidylcholine conferring cone shape with packing parameter greater than one, preferring inverted hexagonal HII phases under stress and reducing bilayer stability. Enrichment of PE in cytoplasmic leaflet promotes formation of fusion intermediates like stalks and hemifusion diaphragms required for SNARE-mediated exocytosis, supports high curvature of endocytic buds and cristae junctions stabilized by ATP synthase dimers and OPA1. Phosphatidylethanolamine is generated from phosphatidylserine decarboxylation by phosphatidylserine decarboxylase PSD in mitochondria inner membrane and via CDP-ethanolamine Kennedy pathway in ER. Cholesterol modulates bending rigidity but induces less curvature than PE, sphingomyelin cylindrical shape stabilizes flat domains. Therefore PE distribution is major lipid factor shaping vesicle budding and organelle morphology during trafficking.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 10: Membrane Curvature and PE Shape.

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Plasma Membrane

Which of the following is NOT a feature of plasma membrane lipids?

Plasma membrane lipids assemble through non-covalent forces rather than covalent polymerization. Each phospholipid or cholesterol monomer inserts via hydrophobic effect with tails buried together while polar headgroups contact water, stabilized by van der Waals contacts, hydrogen bonding between phosphate oxygens and water, and electrostatic interactions. This allows lateral diffusion, rotation, and exchange between leaflets catalyzed by flippases, and reversible desorption to cytosolic carriers. Membranes exhibit selective permeability because polar headgroup region impedes hydrophobic solutes while hydrocarbon core impedes polar solutes, requiring transporters. They self-assemble into bilayers spontaneously when amphipathic lipids reach critical micelle concentration, forming vesicles that encapsulate aqueous contents, principle exploited for liposomal drug delivery. If lipids were covalently bonded together like polymers, fluidity would be lost, proteins could not diffuse, and processes like cell fusion, cytokinesis, and endocytosis would be impossible. Consequently fluidity, repair, and remodeling depend on non-covalent nature, with proteins providing scaffold but not crosslinking lipids permanently.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 10: Non-Covalent Assembly of Lipids.

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Plasma Membrane

Which property of lipid bilayers allows self-repair of membranes?

Spontaneous assembly and healing of lipid bilayers arises from hydrophobic effect, fundamentally entropic driving force where water molecules form highly ordered clathrate-like cages around exposed hydrocarbon, reducing entropy of system. Aggregating acyl chains releases ordered water, increasing bulk water entropy and lowering overall Gibbs free energy by approximately 5 kJ per methylene group, favoring self-association. Van der Waals interactions between parallel acyl chains contribute additional enthalpic stabilization. If membrane suffers pore or tear exposing hydrocarbon edge to water, line tension at edge with exposed aliphatic chains contacting water is thermodynamically highly unfavorable, prompting rapid lateral flow of neighboring phospholipids to seal defect within milliseconds, minimizing hydrocarbon-water contact, process occurring without enzymatic assistance or ATP consumption. This self-repair underlies liposome formation when phospholipids are hydrated and vortexed, recovery after mechanical shearing and electroporation, and fusion of synaptic vesicles where stalk intermediates resolve to maintain continuity. High melting temperature would rigidify chains hindering closure, indicating hydrophobic interactions provide intrinsic resilience essential for maintaining barrier during stress and movement.

Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 7: Hydrophobic Effect and Self-Sealing.

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Plasma Membrane

Which of the following best describes the Fluid Mosaic Model?

Proposed by S.J. Singer and G.L. Nicolson in 1972 based on freeze-fracture electron microscopy and cell fusion experiments, the Fluid Mosaic Model describes membrane as two-dimensional solution where amphipathic lipids form viscous fluid matrix, about 100-fold more viscous than water, within which integral membrane proteins float as mosaic of diverse functions including pumps, receptors, adhesion molecules, and enzymes. Phospholipids exhibit rapid lateral diffusion around 10^-8 cm2 per second, rotation around axis, flexing of chains, but slow transverse flip-flop unless catalyzed by flippases, evidence obtained by Frye-Edidin heterokaryon fluorescence showing intermixing of human and mouse antigens within minutes and later fluorescence recovery after photobleaching revealing mobile fraction. Peripheral proteins attach via electrostatic interactions with anionic headgroups or protein-protein interactions via adapters. Lipid composition variation creates phase coexistence: saturated sphingolipids and cholesterol form ordered microdomains rafts. Mosaic arrangement allows remodeling during endocytosis, formation of immunological synapse, and diffusion-reaction signaling. Membranes are not static crystalline arrays of Davson-Danielli sandwich nor composed solely of phospholipids, but dynamic mosaics enabling compartmentalization and adaptability essential for life.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 10: Fluid Mosaic Model, Singer and Nicolson.

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Plasma Membrane

Which type of lipid is NOT a part of the plasma membrane?

Biological membrane formation is governed by amphipathic geometry where polar headgroup cross-section balances hydrophobic tail volume, satisfying packing parameter close to 1 for bilayer assembly and stability. Phospholipids such as phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, sphingolipids like sphingomyelin and cerebroside, and cholesterol as small amphiphile intercalated among chains all meet this criterion and readily incorporate into 5 nanometer fluid mosaic film with integral proteins diffusing laterally. Triglycerides, triacylglycerols composed of glycerol esterified to three fatty acids lacking phosphate, sugar, or charged moiety, are completely apolar with no amphipathic character, unable to orient with one end in water. In aqueous environment they coalesce into bulk oil phase, phase separating rather than forming lamellae. Cells store triglycerides in lipid droplet organelles comprising neutral hydrophobic core surrounded by phospholipid monolayer decorated with perilipins and seipin, located in cytosol or within ER lumen for VLDL assembly in liver. Adipocytes contain large droplets for energy reserve mobilized by hormone-sensitive lipase and lipolysis. Therefore plasma membrane excludes triglycerides, which would compromise barrier integrity and fluidity.

Ref: Lehninger Principles of Biochemistry, 8th ed., Chapter 10: Triglycerides vs Membrane Lipids.

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Plasma Membrane

What is the role of phosphatidylinositol in the membrane?

Phosphatidylinositol's inositol ring protruding into cytosol can be phosphorylated to produce phosphoinositides that act as transient second messenger precursors. Upon activation of GPCR coupling to Gq or RTK activating PLC-gamma, phospholipase C cleaves PIP2 into diacylglycerol which stays embedded to recruit C1 domain of protein kinase C and Munc13 for exocytosis, and soluble IP3 that binds tetrameric IP3 receptor calcium channels on ER releasing calcium that activates calmodulin and NFAT. Concurrently class I PI3K phosphorylates PIP2 to PIP3 which accumulates transiently and recruits proteins containing PH domain such as Akt, PDK1, and BTK to plasma membrane, triggering Akt-mTOR pathway controlling survival, protein synthesis, and glucose metabolism. Dephosphorylation by PTEN and SHIP phosphatases terminates signal. Additional roles include PI4P at Golgi recruiting adaptors for vesicle budding and PIP2 binding to actin regulators like profilin. Thus PI cycle provides rapid, reversible production of lipid and soluble messengers, distinguishing it from structural roles or ion conduction.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 15: Phosphoinositide Signaling Cascade.

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Plasma Membrane

Which type of membrane transport is facilitated by transmembrane proteins?

Passive entry of polar solutes across 4 nm hydrophobic core is energetically prohibited, necessitating membrane proteins that provide facilitated diffusion pathway without ATP input. Transmembrane proteins create two mechanisms: channel proteins like aquaporin-1, potassium channels with selectivity filter TVGYG, and porins with beta-barrels that form continuous aqueous pores allowing diffusion at rates approaching 10^8 ions per second down electrochemical gradient, gating regulated by voltage, ligand, or mechanical force. Carrier proteins like GLUT1 glucose transporter and AE1 anion exchanger bind solute specifically, undergo conformational inversion from outward-open to inward-open, increasing permeability and specificity while still moving down gradient. Simple diffusion of O2, CO2, and steroid hormones occurs directly through lipid matrix independent of proteins due to high partition coefficient. Passive osmosis follows water activity gradient but accelerated by aquaporins. Lipid bilayer flipping of polar lipids requires flippases and is not spontaneous transport. Hence transmembrane proteins convert impermeable barrier into selective gateway enabling facilitated diffusion essential for nutrient uptake and excitability.

Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 11: Facilitated Diffusion and Transporters.

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Plasma Membrane

Which of the following forms mixed bilayers with phosphoglycerides?

Phosphoglycerides and sphingomyelin can co-assemble into stable mixed bilayers because both possess two hydrophobic tails and cylindrical geometry compatible with lamellar phase, unlike lysophospholipids that form micelles or cardiolipin that favors hexagonal inverted phases due to small headgroup. Sphingomyelin's fatty acid amidated to sphingosine resembles phosphatidylcholine's diacylglycerol moiety in hydrophobic thickness, allowing van der Waals matching and hydrophobic mismatch avoidance, enabling fluid mosaic continuity. Moreover sphingomyelin synthesis itself links the two classes: sphingomyelin synthase SMS1 and SMS2 in Golgi and plasma membrane transfer phosphocholine from phosphatidylcholine onto ceramide producing diacylglycerol signaling lipid activating protein kinase D. In model membranes, sphingomyelin-phosphatidylcholine mixtures exhibit miscibility with cholesterol-induced phase separation into liquid-ordered rafts, explaining outer leaflet enrichment and organization of GPI-anchored proteins. Cholesterol alone is too small with single hydroxyl to form bilayer alone, requiring phospholipid matrix, while phosphatidylinositol prefers inner leaflet due to polyphosphate negative charge. Thus sphingomyelin uniquely partners with phosphoglycerides to build heterogeneous mosaic bilayer with domains.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 10: Mixed Bilayers of Sphingomyelin.

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Plasma Membrane

Which of the following phospholipids is most abundant in the outer leaflet of the plasma membrane?

Quantitative lipidomics using phospholipase treatment, chemical labeling, and mass spectrometry shows outer leaflet of mammalian plasma membrane is dominated by choline-containing lipids: phosphatidylcholine roughly 60% of outer phospholipid and sphingomyelin nearly exclusively outer, together creating relatively neutral, saturated, raft-competent surface that interacts with extracellular environment and immune system. Their cylindrical shape stabilizes flat outer leaflet and protects from opsonization by complement. In contrast phosphatidylserine and phosphatidylethanolamine concentrate 75 to 90% in inner leaflet facing cytosol where their anionic and conical properties facilitate generation of negative curvature for endocytosis, binding of polycationic domains of Ras and annexins including annexin A2, and support for protein kinase C activation. Phosphatidylinositol and its phosphorylated derivatives also inner, providing platform for cytoskeleton attachment via ERM proteins and clathrin adaptors. Cardiolipin with four acyl chains is signature of inner mitochondrial membrane where it binds respiratory complexes, absent from plasma membrane. Therefore phosphatidylcholine outer enrichment reflects active sorting by P4-ATPases and thermodynamic preference, essential for charge asymmetry and signaling integrity.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 10: Outer Leaflet Enrichment of PC.

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Plasma Membrane

Which of the following molecules is the main precursor for sphingolipids?

Building sphingolipids requires creation of sphingoid long-chain base de novo in endoplasmic reticulum membrane through highly regulated steps essential for barrier formation. Serine palmitoyltransferase, heterodimer of SPTLC1 and SPTLC2 regulated by ORMDL feedback inhibition and small subunits ssSPTa/b that determine acyl chain preference, condenses L-serine and palmitoyl-CoA producing 3-ketodihydrosphingosine, reduced by 3-ketodihydrosphingosine reductase KDSR to dihydrosphingosine, also called sphinganine. Dihydrosphingosine is N-acylated by six ceramide synthases CerS isoforms with fatty-acyl specificity ranging C14 to C26 to dihydroceramide and desaturated by dihydroceramide desaturase DES1 to ceramide whose backbone is sphingosine, 2-amino-4-octadecene-1,3-diol. This amino alcohol thus represents defining precursor whose fatty acid chain can be remodeled via salvage pathway where sphingosine generated from sphingomyelin hydrolysis by acid sphingomyelinase is rapidly reacylated. Subsequent phosphorylation by sphingosine kinases 1 and 2 yields sphingosine-1-phosphate high-affinity ligand for S1PR1-5 GPCRs controlling lymphocyte egress from lymph nodes, angiogenesis, and vascular barrier integrity and immune regulation in mammals critically.

Ref: Lehninger Principles of Biochemistry, 8th ed., Chapter 21: Sphingosine Precursor and S1P Signaling.

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Plasma Membrane

Which of the following statements about lipid rafts is correct?

Lipid rafts are defined as transient, nanoscale domains 10-200 nm enriched in saturated sphingolipids including sphingomyelin and glycosphingolipids, cholesterol, and GPI-anchored proteins plus acylated inner leaflet proteins like Src kinases, exhibiting liquid-ordered phase where acyl chains are extended and ordered yet laterally mobile, surrounded by liquid-disordered PC-rich matrix. Their cholesterol dependence arises from hydrogen bonding between cholesterol hydroxyl and sphingolipid amide, plus van der Waals interaction with saturated chains, increasing order and thickness. Importantly rafts are highly dynamic, assembling and disassembling on millisecond timescales, merging upon receptor crosslinking to concentrate signaling components like B cell receptor, LAT in T cells, and endothelial nitric oxide synthase. They do not lack cholesterol nor are restricted to bacteria which lack cholesterol but use hopanoids analogously. Techniques including FRET, super-resolution STED, single-particle tracking, and isolation of detergent-resistant membranes support their existence as platforms for endocytosis, viral entry, and immune synapse organization, regulating protein-protein interactions without requiring higher overall protein density.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 10: Lipid Rafts and Membrane Domains.

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