Plasma membrane

Membrana cellularis; plasmalemma

Also known as: cell membrane, plasmalemma, fluid mosaic model, lipid bilayer, glycocalyx

The ≈8 nm lipid bilayer with embedded proteins that encloses the cell, controls what enters and leaves, and carries receptors, transporters and adhesion molecules.

Overview

Thickness≈7.5–10 nm

Composition (by mass)≈50 % lipid, ≈50 % protein (varies; myelin ≈75 % lipid)

Lipid : protein molecules≈50 : 1

CholesterolUp to ≈1 per phospholipid

The fluid mosaic model (Singer & Nicolson, 1972) describes the membrane as a two-dimensional fluid of amphipathic phospholipids — hydrophilic phosphate heads facing the watery extracellular fluid and cytosol, hydrophobic fatty-acid tails facing each other in the core — in which proteins float and diffuse laterally. Lipids move freely within a leaflet but rarely "flip-flop" between leaflets without enzymes (flippases, floppases, scramblases), so the bilayer is asymmetric: phosphatidylcholine, sphingomyelin and glycolipids are mainly in the outer leaflet; phosphatidylserine, phosphatidylethanolamine and phosphatidylinositol in the inner leaflet. Exposure of phosphatidylserine on the outer leaflet is an "eat me" signal on apoptotic cells and a pro-coagulant surface on activated platelets.

Cholesterol (up to about one molecule per phospholipid) inserts between phospholipids: it stiffens the membrane at body temperature yet prevents it from solidifying in the cold — a fluidity buffer. Cholesterol and sphingolipids cluster with certain proteins into lipid rafts, platforms for signalling and caveolae. Membrane proteins make up about half of the membrane mass: integral (transmembrane) proteins span the bilayer (channels, carriers, pumps, receptors, adhesion molecules); peripheral proteins attach to the surfaces (e.g. spectrin–ankyrin membrane skeleton); lipid-anchored proteins are tethered by fatty-acyl, prenyl or GPI anchors.

The carbohydrate chains of glycoproteins and glycolipids face only the exterior and form the glycocalyx (cell coat), which mediates cell recognition (ABO blood-group antigens, MHC), adhesion and protection, and binds enzymes such as the brush-border disaccharidases of enterocytes.

Location

Surrounds every cell; similar bilayers (without a glycocalyx) bound the intracellular organelles.

Parts & subdivisions

Phospholipid bilayer

Two leaflets of phosphoglycerides and sphingolipids; impermeable to ions and polar molecules, permeable to small non-polar molecules (O₂, CO₂, steroids) and slowly to water.

Cholesterol

Modulates fluidity and permeability; enriched in lipid rafts.

Integral (transmembrane) proteins

Span the bilayer, usually as α-helices of ≈20 hydrophobic amino acids; include channels, carriers, pumps, receptors, integrins and cadherins.

Peripheral proteins

Bound non-covalently to the membrane surface or to integral proteins (e.g. spectrin network on the cytosolic face).

Glycocalyx

Carbohydrate coat of glycoproteins, glycolipids and proteoglycans on the external surface; PAS-positive.

Lipid rafts and caveolae

Cholesterol/sphingolipid-rich microdomains; caveolae are flask-shaped raft invaginations coated by caveolin.

Anatomy

Histology

Too thin (≈7.5–10 nm) to be resolved by light microscopy. With transmission electron microscopy, osmium staining shows a trilaminar "unit membrane" — two electron-dense lines (the hydrophilic heads) separated by a lucent layer (the hydrophobic tails). Freeze-fracture splits the bilayer to reveal intramembrane particles (integral proteins).

Function

Selective barrier separating intracellular and extracellular fluids.

Transport of solutes by channels, carriers and pumps, and of macromolecules by endocytosis and exocytosis.

Generates and maintains the membrane potential.

Signal reception via receptors.

Cell–cell and cell–matrix adhesion (cadherins, integrins) and recognition (glycocalyx).

Anchors the cytoskeleton and determines cell shape.

Physiology

Permeability depends on size and polarity: gases and lipid-soluble molecules diffuse freely; water crosses slowly through the bilayer and rapidly through aquaporins; ions and polar molecules (glucose, amino acids) require transport proteins. See membrane transport and membrane potential.

Clinical significance

Cystic fibrosis

Autosomal recessive mutations of CFTR, a cAMP-regulated Cl⁻ channel of the ABC-transporter family. The commonest mutation (ΔF508) misfolds and is degraded in the ER. Thick secretions obstruct airways, pancreatic ducts and vas deferens; sweat Cl⁻ is raised (> 60 mmol/L).

Paroxysmal nocturnal haemoglobinuria

Acquired PIGA mutation in haematopoietic stem cells prevents synthesis of GPI anchors, so the complement inhibitors CD55 (DAF) and CD59 are absent from blood cells → complement-mediated intravascular haemolysis and thrombosis.

Hereditary spherocytosis

Defects of the membrane skeleton (ankyrin, spectrin, band 3) make erythrocytes lose membrane, become spherical and be destroyed in the spleen.