![Cell membrane detailed diagram en](https://upload.wikimedia.org/wikipedia/commons/d/da/Cell_membrane_detailed_diagram_en.svg)
The fluid mosaic model explains various observations regarding the structure of functional
cell membranes
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
. According to this
biological model, there is a
lipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
(two molecules thick layer consisting primarily of
amphipathic
An amphiphile (from the Greek αμφις amphis, both, and φιλíα philia, love, friendship), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'') properties. Such a compoun ...
phospholipids) in which
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
molecules
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...
are embedded. The phospholipid bilayer gives
fluidity and
elasticity
Elasticity often refers to:
*Elasticity (physics), continuum mechanics of bodies that deform reversibly under stress
Elasticity may also refer to:
Information technology
* Elasticity (data store), the flexibility of the data model and the cl ...
to the
membrane
A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
. Small amounts of
carbohydrates
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or may ...
are also found in the cell membrane. The biological model, which was devised by
Seymour Jonathan Singer
Seymour Jonathan Singer (May 23, 1924 – February 2, 2017) was an American cell biologist and professor of biology, emeritus, at the University of California, San Diego.
Biography
Singer was born in New York City and attended Columbia Univers ...
and
Garth L. Nicolson
Garth L. Nicolson (born October 1, 1943) is an American biochemist who made a landmark scientific model for cell membrane, known as the Fluid Mosaic Model. He is the founder of The Institute for Molecular Medicine at California, and he serves as ...
in 1972, describes the cell membrane as a
two-dimensional liquid A two-dimensional liquid (2D liquid) is a collection of objects constrained to move in a planar or other two-dimensional space in a liquid state.
Relations with 3D liquids
The movement of the particles in a 2D liquid is similar to 3D, but with li ...
that restricts the
lateral diffusion
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (th ...
of membrane components. Such domains are defined by the existence of regions within the membrane with special lipid and protein cocoon that promote the formation of
lipid rafts
The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains somewhat controversial. ...
or protein and
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
complexes. Another way to define membrane domains is the association of the lipid membrane with the
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
filaments and the
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
through membrane proteins.
The current model describes important features relevant to many cellular processes, including:
cell-cell signaling,
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
,
cell division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
, membrane budding, and cell fusion. The fluid mosaic model is the most acceptable model of the plasma membrane. Its main function is to separate the contents of the cell from the exterior.
Chemical makeup
Experimental evidence
The fluid property of functional biological membranes had been determined through
labeling
Labelling or using a label is describing someone or something in a word or short phrase. For example, the label "criminal" may be used to describe someone who has broken a law. Labelling theory is a theory in sociology which ascribes labelling ...
experiments,
x-ray diffraction
X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
, and calorimetry. These studies showed that integral membrane proteins diffuse at rates affected by the
viscosity
The viscosity of a fluid is a measure of its resistance to deformation at a given rate. For liquids, it corresponds to the informal concept of "thickness": for example, syrup has a higher viscosity than water.
Viscosity quantifies the inte ...
of the lipid bilayer in which they were embedded, and demonstrated that the molecules within the cell membrane are dynamic rather than static.
Previous models of biological membranes included the
Robertson Unit Membrane Model
Robertson may refer to:
People
* Robertson (surname) (includes a list of people with this name)
* Robertson (given name)
* Clan Robertson, a Scottish clan
* Robertson, stage name of Belgian magician Étienne-Gaspard Robert (1763–1837)
Place ...
and the
Davson-Danielli Tri-Layer model.
These models had proteins present as sheets neighboring a lipid layer, rather than incorporated into the phospholipid bilayer. Other models described repeating, regular units of protein and lipid. These models were not well supported by microscopy and
thermodynamic
Thermodynamics is a branch of physics that deals with heat, work, and temperature, and their relation to energy, entropy, and the physical properties of matter and radiation. The behavior of these quantities is governed by the four laws of ther ...
data, and did not accommodate evidence for dynamic membrane properties.
![Versuch zum Fluid-Mosaic-Modell](https://upload.wikimedia.org/wikipedia/commons/c/c1/Versuch_zum_Fluid-Mosaic-Modell.png)
An important experiment that provided evidence supporting fluid and dynamic biological was performed by Frye and Edidin. They used
Sendai virus
''Murine respirovirus'', formerly ''Sendai virus'' (SeV) and previously also known as murine parainfluenza virus type 1 or hemagglutinating virus of Japan (HVJ), is an enveloped,150-200 nm in diameter, a negative sense, single-stranded RN ...
to force human and mouse cells to fuse and form a
heterokaryon
A heterokaryon is a multinucleate cell that contains genetically different nuclei. Heterokaryotic and heterokaryosis are derived terms. This is a special type of syncytium. This can occur naturally, such as in the mycelium of fungi during sexual ...
. Using
antibody staining, they were able to show that the mouse and human proteins remained segregated to separate halves of the heterokaryon a short time after cell fusion. However, the proteins eventually diffused and over time the border between the two halves was lost. Lowering the temperature slowed the rate of this diffusion by causing the membrane phospholipids to transition from a fluid to a gel phase. Singer and Nicolson rationalized the results of these experiments using their fluid mosaic model.
The fluid mosaic model explains changes in structure and behavior of cell membranes under different temperatures, as well as the association of membrane proteins with the membranes. While Singer and Nicolson had substantial evidence drawn from multiple subfields to support their model, recent advances in
fluorescence microscopy
A fluorescence microscope is an optical microscope that uses fluorescence instead of, or in addition to, scattering, reflection, and attenuation or absorption, to study the properties of organic or inorganic substances. "Fluorescence microsc ...
and
structural biology
Structural biology is a field that is many centuries old which, and as defined by the Journal of Structural Biology, deals with structural analysis of living material (formed, composed of, and/or maintained and refined by living cells) at every le ...
have validated the fluid mosaic nature of cell membranes.
Subsequent developments
Membrane asymmetry
Additionally, the two leaflets of biological membranes are asymmetric and divided into subdomains composed of specific proteins or lipids, allowing spatial segregation of biological processes associated with membranes.
Cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
and cholesterol-interacting proteins can concentrate into lipid rafts and constrain cell signaling processes to only these rafts. Another form of asymmetry was shown by the work of Mouritsen and Bloom in 1984, where they proposed a
Mattress Model of lipid-protein interactions to address the biophysical evidence that the membrane can range in thickness and hydrophobicity of proteins.
Non-bilayer membranes
The existence of non-bilayer lipid formations with important biological functions was confirmed subsequent to publication of the fluid mosaic model. These membrane structures may be useful when the cell needs to propagate a non bilayer form, which occurs during cell division and the formation of a
gap junction
Gap junctions are specialized intercellular connections between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulate ...
.
Membrane curvature
The membrane bilayer is not always flat. Local curvature of the membrane can be caused by the asymmetry and non-bilayer organization of lipids as discussed above. More dramatic and functional curvature is achieved through
BAR domain
In molecular biology, BAR domains are highly conserved protein dimerisation domains that occur in many proteins involved in membrane dynamics in a cell. The BAR domain is banana-shaped and binds to membrane via its concave face. It is cap ...
s, which bind to
phosphatidylinositol
Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...
on the membrane surface, assisting in
vesicle
Vesicle may refer to:
; In cellular biology or chemistry
* Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane
* Synaptic vesicle
; In human embryology
* Vesicle (embryology), bulge-like features o ...
formation,
organelle
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
formation and cell division. Curvature development is in constant flux and contributes to the dynamic nature of biological membranes.
Lipid movement within the membrane
During the decade of 1970, it was acknowledged that individual lipid molecules undergo free lateral diffusion within each of the layers of the lipid membrane.
Diffusion occurs at a high speed, with an average lipid molecule diffusing ~2 µm, approximately the length of a large
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
l cell, in about 1 second.
It has also been observed that individual lipid molecules rotate rapidly around their own axis.
Moreover, phospholipid molecules can, although they seldom do, migrate from one side of the lipid bilayer to the other (a process known as flip-flop). However, flip-flop might be enhanced by flippase enzymes. The processes described above influence the disordered nature of lipid molecules and interacting proteins in the lipid membranes, with consequences to membrane fluidity, signaling, trafficking and function.
Restrictions to bilayer fluidity
There are restrictions to the lateral mobility of the lipid and protein components in the fluid membrane imposed by the formation of subdomains within the lipid bilayer. These subdomains arise by several processes ''e.g.'' binding of membrane components to the extracellular matrix, nanometric membrane regions with a particular biochemical composition that promote the formation of lipid rafts and protein complexes mediated by protein-protein interactions.
Furthermore, protein-cytoskeleton associations mediate the formation of “cytoskeletal fences”, corrals wherein lipid and membrane proteins can diffuse freely, but that they can seldom leave.
Restriction on lateral diffusion rates of membrane components is very important because it allows the functional specialization of particular regions within the cell membranes.
Lipid rafts
Lipid raft
The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains somewhat controversial. ...
s are membrane nanometric platforms with a particular lipid and protein composition that laterally diffuse, navigating on the liquid bilipid layer. Sphingolipids and cholesterol are important building blocks of the lipid rafts.
Protein complexes
Cell membrane proteins and glycoproteins do not exist as single elements of the lipid membrane, as first proposed by Singer and Nicolson in 1972. Rather, they occur as diffusing complexes within the membrane.
The assembly of single molecules into these macromolecular complexes has important functional consequences for the cell; such as
ion and metabolite transport, signaling,
cell adhesion
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...
, and
migration
Migration, migratory, or migrate may refer to: Human migration
* Human migration, physical movement by humans from one region to another
** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...
.
Cytoskeletal fences (corrals) and binding to the extracellular matrix
Some proteins embedded in the bilipid layer interact with the extracellular matrix outside the cell, cytoskeleton filaments inside the cell, and septin ring-like structures. These interactions have a strong influence on shape and structure, as well as on
compartmentalization. Moreover, they impose physical constraints that restrict the free lateral diffusion of proteins and at least some lipids within the bilipid layer.
When integral proteins of the lipid bilayer are tethered to the extracellular matrix, they are unable to diffuse freely. Proteins with a long intracellular domain may collide with a fence formed by cytoskeleton filaments. Both processes restrict the diffusion of proteins and lipids directly involved, as well as of other interacting components of the cell membranes.
Septins are a family of GTP-binding proteins highly conserved among eukaryotes. Prokaryotes have similar proteins called paraseptins. They form compartmentalizing ring-like structures strongly associated with the cell membranes. Septins are involved in the formation of structures such as, cilia and flagella, dendritic spines, and yeast buds.
Historical timeline
* 1895 –
Ernest Overton
Charles Ernest Overton (1865–1933) was a British physiologist and biologist, now regarded as a pioneer of the theory of the cell membrane.
In the last years of the 19th century Overton did experimental work, allowing the distinction to be drawn ...
hypothesized that cell membranes are made out of lipids.
* 1925 –
Evert Gorter and
François Grendel found that red blood cell membranes are formed by a fatty layer two molecules thick, ''i.e.'' they described the bilipid nature of the cell membrane.
* 1935 –
Hugh Davson
Hugh Davson, Baron Davson (25 November 1909 – 2 July 1996) was an English physiologist who worked on membrane transport and ocular fluids.
Davson was born in Paddington, London, the son of physician Wilfred Maynard Davson and Mary Louisa Scott. ...
and
James Danielli
James Frederic Danielli FRS (1911–1984) was an English biologist.
He was famous for research on the structure and the permeability of cell membranes, developing a physical-chemical model in collaboration with the physiologist Hugh Davson ...
proposed that lipid membranes are layers composed by proteins and lipids with pore-like structures that allow specific permeability for certain molecules. Then, they suggested a model for the cell membrane, consisting of a lipid layer surrounded by protein layers at both sides of it.
* 1957 –
J. David Robertson, based on electron microscopy studies, establishes the "Unit Membrane Hypothesis". This, states that all membranes in the cell, ''i.e.'' plasma and organelle membranes, have the same structure: a bilayer of phospholipids with monolayers of proteins at both sides of it.
* 1972 – SJ Singer and GL Nicolson proposed the fluid mosaic model as an explanation for the data and latest evidence regarding the structure and thermodynamics of cell membranes.
Notes and references
{{DEFAULTSORT:Fluid mosaic
Membrane biology
Organelles
Cell anatomy