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Structures and functions of membranes: Membranes are important in many aspects of cellular structure and function. Early studies showed that membranes formed the boundary between the cell and the environment. Erythrocyte ghosts (empty red blood cells) are good examples of cellular (plasma) membranes, and are used as a model. From these studies, it has become clear that membranes are much more complex than mere boundaries between the cytoplasm an extracellular environment.<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

There are three main functions of membranes:

1. Compartmentation of organelles and enzymes.
2. Regulation of transport.
3. Detection and transmission of signals within and between cells.

The cell membrane has long been known to exchange of material with its environment. This is well illustrated in the processes of exocytosis and endocytosis, where solids are expelled from or taken into cells.

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Endocytosis occurs when a eukaryotic cell ingests an extracellular body.

In 1894, Overton observed that lipophilic (hydrophobic) molecules could enter root hairs, but hydrophilic molecules could not. He concluded that the cells were coated with two lipids: lecithin (a phospholipid, also called phosphatidyl choline) and cholesterol, which accounted for the observed permeability. Modern research shows that phospholipids and cholesterol do make up a large proportion of membrane structure, but that there are also many other components.

Phospholipids are composed of four smaller chemicals. Fatty acids esterified to a glycerol molecule form a hydrophobic "tail" to the molecule, whilst a phosphate group and another group (often choline or serine), is also esterified to the glycerol to form a hydrophilic 'head' to the molecule.

There are several sorts of fatty acid. Lauric, myristic, palmitic and stearic acids are saturated (no multiple bonds), oleic, linoleic, γ-linolenic and arachidonic acids are unsaturated (with 1 to 4 double bonds).

Molecular structure	Name
	Lauric acid: saturated C12
	Myristic acid: saturated C14
	Palmitic acid: saturated C16
	Stearic acid: saturated C18
	Oleic acid: monounsaturated C18
	Linoleic acid: diunsaturated C18
	γ-Linolenic acid: triunsaturated C18
	Arachidonic acid: tetraunsaturated C20

There are also several kinds of polar head groups. The following molecules show the various headgroups esterified to a simple distearyl glycerophosphate:

Molecular structure			Name of head group
		Proton - phosphatidic acid.
	Choline - phosphatidyl choline.
	Ethanolamine - phosphatidyl ethanolamine.
	Serine - phosphatidyl serine
	Inositol - phosphatidyl inositol.
	Glycerol - phosphatidyl glycerol.

Plain phosphatidic acid is negatively charged because of the phosphate group, which is ionised (-PO₄²⁻) at physiological pH. Phosphatidylserine and phosphatidylethanolamine are also negatively charged for this reason (-PO₄⁻-). Phosphatidylcholine has no net charge, because the positive charge on choline cancels the negative on phosphate (-PO₄⁻-CH₂CH₂N⁺(CH ₃)₃).

Membrane phospholipids are amphipathic. The head group, containing e.g. charged phosphate and polar choline, is hydrophilic and water soluble.The tail group, containing a nonpolar fatty acid chain, is hydrophobic (lipophilic) and water insoluble. In unsaturated fatty acids, these chains are kinked, and cannot pack so closely. This increases membrane fluidity.

Models of membranes: Many models have been proposed for biological membranes. This is an (approximate) timeline of these ideas.

Langmuir's monolayers (1920): Langmuir showed that if phospholipids are dissolved in benzene they could be dispersed as a monolayer on the surface of water in a Langmuir trough.

Micelles: If shaken with water, phospholipids (like detergents) will form micelles. These are colloids in an aqueous suspension. Micelles have a hydrophilic outside and hydrophobic inside.

Water is inherently disordered, but when lipids are present, the water molecules have to arrange themselves in a more ordered way. The less order there is in a arrangement, the more likely (∆G = ∆H + T∆S) the arrangement is to happen. The clumping together of fat molecules reduces the amount of water that has to be ordered. The left hand (clumpy) picture has fewer water molecules arranged neatly than the right hand (less clumpy) picture.

Gortner & Grendel's bilayers (1925): These researchers extracted the lipid from the plasma membrane of RBCs and applied them to a Langmuir trough. They covered twice the area of the original membrane showing that natural membranes are bilayers.

Liposomes: If lipids are sonicated at 20 kHz they form vesicles (liposomes) with an internal space.These can be used to deliver hydrophobicdrugs to cells, and as model cells.

Black lipid membranes (1930): Produced by forcing a membrane with a small hole in it through a monolayer in a Langmuir trough. Natural and black lipid membranes have similar thicknesses (c. 7 nm), but natural membranes are generally far more conductive. This indicates there's something else in natural membranes besides lipid.

The composition of membranes reflects their specialisations: nerve cell membranes contain non-conductive lipid, mitochondria contain significant amounts of protein (respiratory complexes).

Source	Protein (%w/w)	Lipid (%w/w)	Carbohydrate (%w/w)
Myelin nerve sheath	18	79	3
Erythrocyte	49	43	8
Chloroplast	70	30	0
Mitochondrion (inner)	76	24	0

Davison & Danielli's sandwich (1935): The earliest true model of membranes proposed a phospholipid bilayer covered in a globular protein coat.

Robertson's unit membrane: Under the electron micrograph, this model appears acceptable: 7 nm thick, with lipid in the middle (white) and protein on outside (black). But freeze-fracture scanning electron micrographs showed things inconsistent with the unit membrane, such as pores and pits. This micrograph was prepared by freezing a cell, then fracturing it with a sharp blow. The forces holding the leaflets of a membrane together are quite weak, so freeze fracture often pulls the two leaflets apart, allowing you to see the proteins that span the membrane very clearly.

Singer-Nicholson fluid mosaic (1972): The fluid mosaic model pictures the membrane as a phospholipid bilayer with many proteins, some integral to the membrane, others attached more loosely. Note the many other components, such as cholesterol; and the attachement sites for the extracellular environment (via glycoproteins) and intracellular cytoskeleton.

Membrane construction: Many proteins participate in the structure and function of membranes. They may be broadly classified as those that are tightly bound (integral) and those that are loosely bound (peripheral).

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