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Phospholipids are lipids containing a phosphate group as part of their structure linked by covalent bonds. The familiar membrane-forming phospholipids are amphiphilic: a hydrophilic head region with chemical polarity coexists with a hydrophobic, largely nonpolar hydrocarbon region. These descriptions refer to different parts of the same molecule, not to two separate substances. See IUPAC Gold Book: phospholipids and IUPAC Gold Book: amphiphilic.

A typical two-chain glycerophospholipid provides a useful example: a glycerol scaffold carries two fatty acid-derived acyl groups through ester linkages, plus a phosphate-containing head region. Phosphatidylcholine is one example. This scaffold describes an important subclass, rather than all phospholipids: sphingomyelin has a different backbone, and even glycerophospholipids need not all have two acyl groups. See IUPAC–IUB, Nomenclature of Lipids (1976), Lip-1.5 and Lip-2.1–2.6.

Polar does not mean negatively charged overall. At near-neutral pH, phosphatidylcholine is zwitterionic: its phosphate region carries negative electric charge and its choline region positive electric charge, with zero net electric charge for the molecule. Counting those opposite charges gives $(-1)+(+1)=0$; it does not remove their local interactions with water. See Lodish et al., Molecular Cell Biology: membrane lipids.

In a lipid bilayer, two membrane leaflets orient their hydrophilic heads toward the water on either side and their hydrophobic chains toward the shared interior. The hydrophobic effect helps explain this organization through the free energy of the water and lipids together. It is not a special repulsive chemical bond between chains and water. Which organization is favored also depends on molecular geometry, temperature, concentration, and the surrounding chemical solution; a phospholipid label alone does not guarantee a lipid bilayer. See Alberts et al., Molecular Biology of the Cell: the lipid bilayer.

This organization supplies a flexible barrier for compartments. A fluid lipid bilayer allows lipids to undergo diffusion within each membrane leaflet; barrier function therefore coexists with motion of molecules, as in the fluid mosaic model. It is not completely impermeable: small nonpolar molecules such as molecular oxygen and carbon dioxide cross much more readily than ions. In a cell membrane, ion channels and other membrane transport proteins provide selective routes; the existing membrane transport article explains their driving forces. See Alberts et al.: principles of membrane transport.

In 1925, E. Gorter and F. Grendel extracted lipids from red blood cells and compared the surface area of a one-molecule-thick film on water with the estimated total surface area of the red blood cells. Their table gave ratios near two, supporting a two-layer covering; they also proposed heads facing the aqueous surroundings on both sides. The inference depends on recovering the relevant lipids, estimating the red blood cell surface area correctly, and comparing compatible packing in the film and the cell membrane. It was indirect evidence, not an image of the lipid bilayer. The paper itself notes possible losses during evaporation. See Gorter and Grendel, On Bimolecular Layers of Lipoids on the Chromocytes of the Blood, Journal of Experimental Medicine 41 (1925), 439–443.

A proteasome is a protein complex that carries out proteolysis; unlike a lysosome, it has no surrounding lipid bilayer.

A proteoliposome is a liposome containing one or more reconstituted membrane proteins in its lipid bilayer. It combines a controlled membrane boundary with a chosen molecular machine. A solution containing detergent-solubilized protein is not automatically a proteoliposome: a closed vesicle and a membrane-incorporated protein must actually be formed.

The artificial compartment is useful because material can be placed on one side of a lipid bilayer and transport measured across it. In an originating experiment on the NhaA sodium/proton antiporter, purified protein was reconstituted into sodium-loaded proteoliposomes. Parallel sodium and proton flux measurements, together with an independent membrane-potential equilibrium method, supported a stoichiometry of two protons per sodium ion over the tested pH range 7.2–8.1.^[ref]

For a bookkeeping example,100 sodium ions moved outward through a perfectly coupled $2{\mathrm{H}}^{+}/\mathrm{N}{\mathrm{a}}^{+}$ exchanger would accompany 200 protons moving inward. The net movement is 100 positive elementary charges inward, which explains the word electrogenic. These invented counts illustrate coupling, not a measured single-vesicle trace.

Interpreting a proteoliposome assay still requires knowing which way the membrane protein faces, whether the vesicles leak, and how much protein is incorporated. An otherwise matched empty liposome helps estimate membrane background. Reconstitution simplifies a biological system; it does not automatically eliminate every alternative source of the measured flux.

The Sec61 complex supports passage across the endoplasmic reticulum membrane and lateral entry of membrane-spanning segments into its lipid bilayer.^[ref]

Secretory protein routing connects entry into the endoplasmic reticulum, protein folding and sorting, transfer to the Golgi apparatus, and delivery onward. In the conventional soluble-cargo route, transport vesicles carry lumenal contents between compartments; exocytosis releases cargo outside the cell membrane. Resident endoplasmic reticulum proteins can be retained or retrieved, and defective cargo can be held back. Many cytosol proteins never enter this route.^[ref]

The useful geometric rule is preservation of membrane sides: during budding and fusion, a lumen-facing region of a membrane protein stays lumen-facing, then faces the exterior after exocytosis; its cytosol-facing region stays cytosolic.^[ref]

Work through the schematic using two distinguishable labels A and B on a stipulated membrane protein. Start with A facing the ER lumen and B facing the cytosol. At each budding or fusion step, carry the surrounding membrane together with the labels; do not turn the protein over. The resulting pair is A facing the Golgi apparatus interior and B facing the cytosol, then A facing a transport vesicle interior and B facing the cytosol, and finally A facing the exterior and B facing the cytosol. This is a stepwise argument about the depicted operations, not a claim that the compartments have identical chemical contents. Likewise, once soluble cargo is inside the ER lumen, this schematic reaches the exterior with zero further crossings through a lipid bilayer: enclosed spaces join when membranes fuse. Delivery therefore need not mean repeatedly pushing a folded protein through a membrane.

Selective permeability means that a cell membrane permits different substances to pass at different rates under comparable conditions. Both the lipid bilayer and the available membrane proteins contribute to this selection.

Artificial boundaries can also have selective permeability. For osmosis, specify which solutes cross and over what observation interval: a boundary that retains one solute need not retain another. A semipermeable membrane is the ideal solvent-only boundary used in the osmotic pressure calculation.

Steven D. Marlin is a researcher whose work helped identify a molecular pair involved in cell adhesion. In a 1987 study with T. A. Springer, Steven D. Marlin tested whether purified ICAM-1 could bind biological cells carrying LFA-1.^[ref]

The investigators incorporated purified ICAM-1 into artificial supported lipid bilayers. Cells carrying LFA-1 bound, while the negative comparison cells did not. Antibodies against either partner inhibited the interaction when applied to the corresponding surface.^[ref]

Reconstitution narrowed the explanation. Adhesion between two intact biological cells might depend on many surface components; supplying one purified candidate in an artificial membrane reduced that complexity. Blocking each side independently then tested whether both identified proteins contributed to the measured attachment.

Synaptobrevin is a membrane-anchored SNARE protein associated with secretory vesicles, including synaptic vesicles. Its cytosolic helix joins complementary helices from syntaxin and SNAP-25 to form a SNARE complex. When the partners initially occupy opposing lipid bilayers, their assembly helps bring those lipid bilayers close enough for membrane fusion. The protein helps couple the membranes mechanically; it is not a pore through which the neurotransmitter simply leaks. ^[ref]

Reconstituting synaptobrevin and its complementary SNARE proteins into separate liposomes made fusion measurable outside a cell. The ability to accumulate docked intermediates at low temperature and trigger fusion on warming also distinguished membrane docking from the subsequent merger. Living synapses add regulation that this minimal assay does not reproduce. ^[ref]

Syntaxin is a family of membrane-anchored SNARE proteins that contributes a helix to a membrane-fusion complex. In neuronal secretion, syntaxin and SNAP-25 on the target cell membrane assemble with synaptobrevin on a synaptic vesicle. Syntaxin contributes one helix, synaptobrevin one and SNAP-25 two, producing a four-helix SNARE complex from three protein chains. Assembly across opposing lipid bilayers couples molecular binding to membrane fusion. ^[ref]

The membrane context matters. Reconstituted complementary SNARE proteins in different liposomes can promote fusion, while a complex assembled after fusion has its membrane anchors on the same lipid bilayer. Detecting a syntaxin-containing complex therefore does not by itself show that it is still bridging a vesicle to its target. ^[ref]

A transmembrane protein has at least one polypeptide chain crossing the complete lipid bilayer. One crossing is single-pass; several crossings in one chain are multipass. Hydrophobic regions face the membrane interior, while hydrophilic regions can face water.^[ref]

A trans-SNARE complex links SNARE proteins anchored in different lipid bilayers. Its formation can bring membranes together before complete membrane fusion.

In an incompressible, noninterdigitating lipid bilayer with negligible head-group thickness, let the inner radius be $r>0$, molecular tail volume $v>0$ and head-group area $a>0$. Counting heads on both membrane leaflets and conserving tail volume gives $R^3-r^3=3(v/a)(R^2+r^2)$. For $R>r$, the function $q(R)=(R^3-r^3)/(R^2+r^2)$ has derivative $(R^4+3R^2{r}^2+2R{r}^3)/(R^2+r^2{)}^2>0$, starts at zero and tends to infinity. Thus exactly one candidate outer radius exists in this geometric model. A maximum tail length $l$ additionally requires $r_m-r\le l$ and $R-r_m\le l$, where $r_m^3=r^3+3(v/a)r^2$. Uniqueness does not establish compatibility with arbitrary molecular lengths.

A vesicle is a small compartment enclosed by a lipid bilayer. Its vesicle lumen can carry soluble cargo, while its lipid bilayer carries lipids and membrane proteins. In a transport pathway, budding separates a carrier from one compartment and membrane fusion joins it to another. Orientation matters: fusion of a secretory vesicle with the cell membrane connects its vesicle lumen to the extracellular space while incorporating its membrane proteins into the surface. ^[ref]

A vesicle is therefore more than a freely diffusing package. Recognition, movement and membrane fusion require distinct interactions. In a reconstitution experiment, complementary SNARE proteins placed in separate liposomes brought opposing lipid bilayers together and promoted fusion; the experiment isolated one part of transport from the rest of a living cell. ^[ref]

The vesicle lumen is the enclosed interior of a vesicle, separated from the cytosol by its lipid bilayer. It can contain dissolved cargo, ions and portions of membrane proteins facing inward. In a synaptic vesicle, for example, the neurotransmitter is stored in the vesicle lumen before exocytosis.

Membrane topology makes this interior useful to track. When a vesicle buds from the endoplasmic reticulum, its vesicle lumen derives from the interior of the endoplasmic reticulum; fusion with the Golgi apparatus delivers the cargo into the next lumen without exposing it to the cytosol. When a secretory vesicle undergoes exocytosis, the vesicle lumen opens to the extracellular space. Thus an enclosed compartment can transport material through a biological cell while keeping it on the same side of a cell membrane throughout.^[ref]

Wolfgang Helfrich developed a continuum description of how lipid bilayers store elastic energy when bent. His 1973 theory distinguishes curvature, stretching and tilt, and relates the shapes of closed vesicles to curvature elasticity. In modern notation its bending contribution iswhere $H$ is mean curvature, $K$ is Gaussian curvature, $C_0$ is the preferred sum of principal curvatures associated with spontaneous curvature, and $\kappa ,\bar{\kappa }$ are elastic coefficients. The model explains how a flexible membrane can prefer a shape even without a rigid supporting skeleton.^[ref]