List of abbreviations
Every attempt was made to provide correct information and labelling, however any liability for eventual errors or incompleteness is rejected!
|2 cell membranes and
intercellular space (rat)
|freeze fracture image of a
human erythrocyte membrane
|stacks of membranes of an
outer segemnet of a rod (rat)
|infolding of the membrane
in endocytosis (rat)
|thickened outer layer of the cell
membrane in urinary bladder (rat)
|cell membrane of
an erythrocyte (rat)
|cell membrane of a
|microvilli with glycocalix coat on
a human cell membrane
|protrusion of the cell membrane
in form of a microvillus (human)
|human microvilli in
|digitations = interdigitated
cell membranes (rat)
|myelin sheath consisting of multiple
layers of cellular membrane (rat)
|cell membrane at
human node of Ranvier
|ureter: formation of
|such vesicles in a super-
ficial cell of pig ureter
|irregular surface of
superficial cell (pig)
|plaque attached to the cell mem-
brane in a hemidesmosome (rat)
|stable connection of cells involving cell
membrane: desmosomes, human skin
formation ureter (pig)
|detail: thickened outer layer
of the cell membrane ureter (pig)
|disruption of the membrane during
secretion of a goblet cell (rat)
|neurotransmission in a synapse
happens on the cell membrane (rat)
|receptors in cell membrane
are required for olfaction (rat)
|tight junction of cell membranes
basis for blood liquor barrier (rat)
|keratinized squamous epithelial cell with thickened
cell membrane of esophagus (rat)
|very closely attached cell mem-
branes with channels in a nexus (rat)
The cell membrane (Terminologia histologica: Plasmalemma;
Membrana cellularis) also called plasmalemma or cytomembrane
is a biological unit membrane, i.e. is a double-membrane.
It constitutes the outer border of all cells in humans and animals limiting the (interior) cellular space, i.e. the cytoplasm or cellular body with its organells which is also called intracellular space to the surrounding extracellular space. The cell membrane is too small to be visible with a light microscope due to its thickness of only 6 to 9 (mostly 8) nm. Nevertheless this small elastic "skin" of the cell is rather solid.
As biological unit membrane the cell membrane consists of lipids and proteins which may be connected to sugars and linked to its surface as glycolipids or glycoproteins to form an additional layer, the glycocalyx. The relation of lipids to proteins ranges from 4 : 1 to 1 : 4 and depends on the kind of the cell and its metabolic activity. Most of the lipids involved in cell membrane construction are phospholipids which are further classified as glycerophosphatids (phosphatidylethanolamin, phosphatidylcholin, phosphatidylserin) and sphingophosphatids (sphingomyelin, cerebrosids, gangliosids). Additionally cholesterin is present as neutral lipid. The outer part of the cellular membrane mainly shows glycoproteins and glycolipids or sphingomyelin and phosphatidylcholine whereas the inner membrane has a highe amount of phosphatidylethanolamin; phosphatidylserin is only seen in the inner layer. Most of the lipids have a polarhead part which is hydrophilic, i.e. has a high affinity for water while being rejectant to lipids, i.e. lipophobic. The apolar tail part of lipids is formed by 2 long fatty acid chains (one of which often is insaturated) and is rejectant to water, i.e. hydrophobic but lipophilic, i.e. attacting lipids. Thus the whole lipid has an amphitathic character meaning that both molecular ends show opposing affinities. When a larger amount of such molecules comes into a waterly medium as it is present in the body, they arrange to spherical bodies spontanously. These spheres are partly micells and partly liposomes. Liposomes are spherical arrangements of amphipathic lipids in which the hydrophilic head parts are directed outwards while the ends of the tails are oriented to the interior. Micells are also spherical arrangements but of a double membrane that encloses a little fluid. Their composition is as follows: hydrophilic head parts are directed outwards side by side, in the mid region the lipophilic tail ends of the two layers are touching each other and the hydrophilic heads of the 2nd membrane layer are oriented to the interior which contains waterly medium;
briefly: outwards - heads of lipid 1 - tail of lipid 1 - tail of lipid 2 - head of lipid 2 - inner space of the micell.
The cell membrane is similar to a micell but further has a lot of different associated or integrated proteins. The latter are either peripherical or integral. Peripherical proteins are electrostatically bound to the outer polar heads of the lipids of the cell membrane, thus they are either attached to the outer surface or the cytoplasmic surface of the membrane. Integral proteins reach with hydrophipic molecule areas into the hydrophibic central area of the double-membrane. Dependent on their molecular composition large proteins may reach through the entire membrane and show parts on the outer as well as inner membrane surface. Such proteins are called transmembrane proteins. In many cases such proteins form a minute pore in their interior which connects the extra- to the intracellular space allowing entry of water or ions into the cell or the contrary, i.e. allow water / ions to leave the cell. Such ion channels are of special importance for exicitatory processes and conductance e.g. in smooth or heart muscle cells. The opening and closure of all such tunnel proteins is well controlled, mostly specific for one or two kinds of ions and combined with a change of their three-dimensional structure. In some cases the transported substrate alone e.g., glucose after binding to a specific extramembrane area of the protein opens the channel in other cases a further (mostly hormoneal) signal is required for channel activation.
All components of the cellular membrane are free free floating, i.e. may move freely in any direction resulting in a fluid mosaic membrane model. The movement increases with temperature. At low temperatures cell membranes are thinner (6 nm) and have a gel-like consistency whereas at high temperatures membrane thickness may raise to 9 nm and the consistency gets sol-like. At normal body temperature cellular membranes are ~8 nm thick and sol-like.
Electron microscopic composition:
Electron microscopic examination shows 3 layers of the cell membrane:
- outwards, i.e. at the outer or superficial surface (Terminologia histologica: Facies externa) a 2.5 nm thick external electron-dense lamina (Terminologia histologica: Lamina densa externa) consisting of the hydrophilc portions of the lipids with integrated or attached proteins. At some cells a glycocalyx (Terminologia histologica: Glycocalyx) consisting of sugars and attached proteins is anchored to the external cellular membrane and reaches into the extracellular space. In freeze-etching preparations where a specimen is broken by special aparatuses this outer face of the cell membrane is called E-face, external fractured face or exoplasmic face (Terminologia histologica: Facies E; Facies fracta externa).
- in the centre a 3 nm strong hardly electron-dense layer, the middle lucent lamina (Terminologia histologica: Lamina intermedia lucida) in which the hydrophobic ends of the lipids and hydrophobic regions of transmembrane proteins are located. Rarely intramembrane particles, i.e. fine electron-dense granules (Terminologia histologica: Granula intramembranacea), protrusions of intramembrane particles (Terminologia histologica: Protrusiones granulorum intramembranaceorum) or rare impressions of intramembrane particles (Terminologia histologica: Impressiones granulorum intramembranaceorm) are seen in this area.
- the inner lamina inner surface or cytosolic face which is directly bordering the cytoplasm (Terminologia histologica: Facies interna) is a 2.5 nm thick internal electron-dense lamina (Terminologia histologica: Lamina densa interna). Filaments of the cytoskeleton are anchored to the proteins of this lamina. In freeze-etching preparations this face of the cell membrane is called protoplasmic fractured face; P face (Terminologia histologica: Facies P; Facies fracta cytoplasmica; Facies fracta protoplasmica).
One image above shows such a freeze etching preparation. Hereby the double membrane is broken in the central area where the tails of the lipids hit each other, thus the outer (exoplasmatic = E-face) and the inner (protoplasmatic = P-face) get apparent. Using this technique the broken transmembrane proteins and fine regular tails of the lipids may be differentiated.
- The cell membrane is a border between the extra- and the intracellular space which show considerable differences in composition. All substances that enter or leave cells have to pass or need to be transported throgh it. Cell membranes are semipermeabel, i.e. allow only few substances with certain chemical behaviour to pass. Small lipophilic molecules e.g., steroid hormones and hormones of the thyroid gland may directly pass the plasmalemm, whereas all larger or hydrophilic substances require special transport mechanisms which usually base on more or less specific proteins that mostly require energy for such active transport processes.
- The shape of cell membranes follows changes of the cytoskeleton and plastically adapts to them e.g., when processes or pseudopods are newly formed or redrawn into the soma in freely moving cells. Cell membrane material may be transported throgh the whole cell to an opposite side via vesicles.
- electric impulses spread along the cell membrane which is of major importance in nerve cells and their processes.
- The glycocalyx which is present on most cells is very important for cell recognition by the immune system and the morphological substate of blood groups.
- The integral proteins of the inner lamina of the cell membrane bind to filaments of the cytoskeleton to preserve stability of the whole cell.
- The functions of cells are influenced by extracellular signals which are the targets of lots of receptors mostly located on the surface of the cell membrane.
In fact most of the membrane bound proteins serve as receptors for mostly highly specific substrates (ligands). This means that only very few substances with very special chemical and structural components are able to interact with the receptor molecules. There are many classes of receptors e.g., receptors for cellular growth and differentiation, receptors for neurotransmitters (of nerve cells), immunological receptors for cell recognition, for viruses or bacterial toxins, receptors to which pharmaca bind. On the cytoplasmatic face of the cell membrane receptors with affinity to cytoplasmatic filaments predominate. The binding of a ligand to its receptor results in a structural change of the latter which causes different kinds of effects:
A. signal transduction: The three-dimensional structure of the receptor protein is altered by the specific interaction. Three different kinds of such changes are known:
Type 1 proteinphosphorylation with tyrosinkinase: after binding of the ligand the changed transmembrane receptor activates another protein at the cytoplasmic side under ATP consumption e.g., the insulin receptor;
Type 2 ligand activated ion channel e.g., a neurotransmitter like acetylcholin opens a sodium channel at a synapse;
Type 3 G-protein mediated release of a second messenger like e.g., cyclic Adenosinmonophosphate (c-AMP), Innositoltriphosphate (IP3) or cyclic Guanosinmonophosphate (c-GMP), in these cases intermolecular processes with neighbouring proteins cause activation of an enzyme located on the cytoplasmic surface of the plasmalemm.
B. receptor induced Endocytosis: At this occasion a small invagination of the cell membrane allows intake of extracellular fluid and molecules by formation of a vesicle which further migrates into the cytoplasm.
cell membrane junctions:
In epithelia cells are connected to each other via different intercellular junctions to ensure tissue stability. The cell membrane is involved in formation of such cell-to-cell connections. Besides interdigitations of cell membranes the following special contacts occur: Zonula occludens and adhaerens, Fascia adhaerens as well as Nexus and Desmosome.
surface differentiations of cells:
Cells can effectively raise their surface area by protrusions of their membranes which can be seen in resorbing epithelia. Depending on morphology and function plasmalemma-coated cell protrusions like immotile microvilli or stereocila can be differentiated from mobile processes like kinocilia, cilia and pseudopods. The uppermost coating cells of transitional epitelia e.g., ureter or urinary bladder, show a very electron-dense and thick outer lamina of their surface membrane towards the lumen. At synapses pre- and postsynaptic densities are attached to the cell membrane. In smooth muscle cells, endothelial cells and hair cells small round dips of the extracellular space into the cytoplasm, the caveols are typical. In rods and cones of the retina dense membrane stacks deriving from the plasmalemm bind the visual pigments.
--> cell surface specialisations, microvilli,
contacts, synapse, gap
junction, tight junction
--> Electron microscopic atlas Overview
--> Homepage of the workshop
One image was kindly provided by HSD Dr. Klinger; other images, page & copyright H. Jastrow.