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{{Short description|Describe the fluid mosaic model of plasma membrane}}
[[File:Cell membrane detailed diagram en.svg|thumb|390px|Fluid mosaic model of a [[cell membrane]]]]

The '''fluid mosaic model''' explains various characteristics regarding the structure of functional [[cell membranes]]. According to this [[Scientific model|biological model]], there is a [[lipid bilayer]] (two molecules thick layer consisting primarily of [[Amphiphile|amphipathic]] phospholipids) in which [[protein]] [[molecules]] are embedded. The phospholipid bilayer gives [[Membrane fluidity|fluidity]] and [[Elasticity (physics)|elasticity]] to the [[membrane]]. Small amounts of [[carbohydrates]] are also found in the cell membrane. The biological model, which was devised by [[Seymour Jonathan Singer]] and [[Garth L. Nicolson]] in 1972,<ref name="Singer1972" /> describes the cell membrane as a [[two-dimensional liquid]] where embedded proteins are generally randomly distributed. For example, it is stated that "A prediction of the fluid mosaic model is that the two-dimensional long-range distribution of any integral protein in the plane of the membrane is essentially random."<ref name="Singer1972" /> 

==Chemical makeup==
{| class="wikitable"
|+
!Components
!Location
!Functions
|-
|Phospholipid
|The main fabric of plasma membrane. Derived from fatty acids, joined by an alcohol residue
|It provides selective permeability to the cell membrane.
The hydrophilic phosphate side is outwards and hydrophobic inwards.  
|-
|Carbohydrates
|Attached to proteins on outside membrane layers
|It helps in cell-to-cell recognition.
|-
|Cholesterol
|Between phospholipids and phospholipid bilayers
|It helps the plasma membrane to retain its fluidity.
|-
|Proteins
|Embedded within or on the surface of phospholipid layers
|These form channels to allow the movement of molecules. 
|}

==Experimental evidence==
The fluid property of functional biological membranes had been determined through [[spin label|labeling]] experiments, [[X-ray crystallography|x-ray diffraction]], and calorimetry. These studies showed that integral membrane proteins diffuse at rates affected by the [[viscosity]] of the lipid bilayer in which they were embedded, and demonstrated that the molecules within the cell membrane are dynamic rather than static.<ref name="Singer1972">{{cite journal | vauthors = Singer SJ, Nicolson GL | title = The fluid mosaic model of the structure of cell membranes | journal = Science | volume = 175 | issue = 4023 | pages = 720–731 | date = February 1972 | pmid = 4333397 | doi = 10.1126/science.175.4023.720 | bibcode = 1972Sci...175..720S | s2cid = 83851531 }}</ref>

Previous models of biological membranes included the [[doi:10.1085/jgp.52.1.257|Robertson Unit Membrane Model]] and the [[Davson–Danielli model|Davson-Danielli]] Tri-Layer model.<ref name="Nicolson2014">{{cite journal | vauthors = Nicolson GL | title = The Fluid-Mosaic Model of Membrane Structure: still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 1838 | issue = 6 | pages = 1451–1466 | date = June 2014 | pmid = 24189436 | doi = 10.1016/j.bbamem.2013.10.019 | doi-access = free }}</ref> 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]] data, and did not accommodate evidence for dynamic membrane properties.<ref name="Nicolson2014"/>

[[File: Versuch zum Fluid-Mosaic-Modell.png|thumb|The Frye-Edidin experiment showed that when two cells are fused the proteins of both diffuse around the membrane and mingle rather than being locked to their area of the membrane.]]
An important experiment that provided evidence supporting fluid and dynamic biological was performed by Frye and Edidin. They used [[Sendai virus]] to force human and mouse cells to fuse and form a [[heterokaryon]]. Using [[Immunostaining|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.<ref>{{cite journal | vauthors = Frye LD, Edidin M | title = The rapid intermixing of cell surface antigens after formation of mouse-human heterokaryons | journal = Journal of Cell Science | volume = 7 | issue = 2 | pages = 319–335 | date = September 1970 | pmid = 4098863 | doi = 10.1242/jcs.7.2.319 }}</ref> Singer and Nicolson rationalized the results of these experiments using their fluid mosaic model.<ref name="Singer1972"/>

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]] and [[structural biology]] 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]] and cholesterol-interacting proteins can concentrate into lipid rafts and constrain cell signaling processes to only these rafts.<ref>{{cite journal | vauthors = Silvius JR | title = Partitioning of membrane molecules between raft and non-raft domains: insights from model-membrane studies | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1746 | issue = 3 | pages = 193–202 | date = December 2005 | pmid = 16271405 | doi = 10.1016/j.bbamcr.2005.09.003 | doi-access =  }}</ref> Another form of asymmetry was shown by the work of Mouritsen and Bloom in 1984, where they proposed a [[Hydrophobic mismatch#Mattress model|Mattress Model]] of lipid-protein interactions to address the biophysical evidence that the membrane can range in thickness and hydrophobicity of proteins.<ref>{{cite journal | vauthors = Mouritsen OG, Bloom M | title = Mattress model of lipid-protein interactions in membranes | journal = Biophysical Journal | volume = 46 | issue = 2 | pages = 141–153 | date = August 1984 | pmid = 6478029 | pmc = 1435039 | doi = 10.1016/S0006-3495(84)84007-2 | bibcode = 1984BpJ....46..141M }}</ref>

===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]].<ref>{{cite journal | vauthors = van den Brink-van der Laan E, Killian JA, de Kruijff B | title = Nonbilayer lipids affect peripheral and integral membrane proteins via changes in the lateral pressure profile | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 1666 | issue = 1–2 | pages = 275–288 | date = November 2004 | pmid = 15519321 | doi = 10.1016/j.bbamem.2004.06.010 | doi-access = free }}</ref>
 
===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]]s, which bind to [[phosphatidylinositol]] on the membrane surface, assisting in [[Vesicle (biology and chemistry)|vesicle]] formation, [[organelle]] formation and cell division.<ref>{{cite journal | vauthors = Frost A, Unger VM, De Camilli P | title = The BAR domain superfamily: membrane-molding macromolecules | journal = Cell | volume = 137 | issue = 2 | pages = 191–196 | date = April 2009 | pmid = 19379681 | pmc = 4832598 | doi = 10.1016/j.cell.2009.04.010 }}</ref> Curvature development is in constant flux and contributes to the dynamic nature of biological membranes.<ref>{{cite journal | vauthors = Rodríguez-García R, Arriaga LR, Mell M, Moleiro LH, López-Montero I, Monroy F | title = Bimodal spectrum for the curvature fluctuations of bilayer vesicles: pure bending plus hybrid curvature-dilation modes | journal = Physical Review Letters | volume = 102 | issue = 12 | pages = 128101 | date = March 2009 | pmid = 19392326 | doi = 10.1103/PhysRevLett.102.128101 | bibcode = 2009PhRvL.102l8101R }}</ref>

===Lipid movement within the membrane===
During the 1970s, it was acknowledged that individual lipid molecules undergo free lateral diffusion within each of the layers of the lipid membrane.<ref name="Alberts">{{cite book |vauthors=Alberts B, Johnson A, Lewis J |title=Molecular Biology of the Cell |edition=5th |pages = 621–622 |isbn=978-0-8153-4105-5 |year=2008 |url=http://www.garlandscience.com/garlandscience_resources/book_resources.jsf?isbn=9780815341055&landing=student |publisher=Garland Science |location=New York|display-authors=etal}}</ref> Diffusion occurs at a high speed, with an average lipid molecule diffusing ~2μm, approximately the length of a large [[bacteria]]l cell, in about 1 second.<ref name="Alberts"/> It has also been observed that individual lipid molecules rotate rapidly around their own axis.<ref name="Alberts"/> 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 movement is enhanced by flippase enzymes.<ref>{{cite journal | vauthors = Hankins HM, Baldridge RD, Xu P, Graham TR | title = Role of flippases, scramblases and transfer proteins in phosphatidylserine subcellular distribution | journal = Traffic | volume = 16 | issue = 1 | pages = 35–47 | date = January 2015 | pmid = 25284293 | pmc = 4275391 | doi = 10.1111/tra.12233 }}</ref> 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 lateral diffusion==
{{Unbalanced section|date=December 2024}}
There are restrictions to the lateral mobility of the lipid and protein components in the fluid membrane imposed by zonation. Early attempts to explain the assembly of membrane zones include the formation of lipid rafts and “cytoskeletal fences”, corrals wherein lipid and membrane proteins can diffuse freely, but that they can seldom leave.<ref name="Nicolson2014"/> These ideas remain controversial, and alternative explanations are available such as the proteolipid code.<ref>{{cite web |last1=Christie |first1=William (Bill) W. |title=Sphingolipids, Membrane Rafts and Caveolae - sphingomyelin and cholesterol - structure, occurrence, biochemistry and function |url=https://lipidmaps.org/resources/lipidweb/lipidweb_html/lipids/sphingo/sph-rafts/index.htm |website=lipidmaps.org |access-date=14 September 2024 |language=en-gb}}</ref>

===Lipid rafts===
[[Lipid raft]]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.<ref>{{cite journal | vauthors = Lingwood D, Simons K | title = Lipid rafts as a membrane-organizing principle | journal = Science | volume = 327 | issue = 5961 | pages = 46–50 | date = January 2010 | pmid = 20044567 | doi = 10.1126/science.1174621 | bibcode = 2010Sci...327...46L | s2cid = 35095032 }}</ref>
 
===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.<ref name="Nicolson2014"/> The assembly of single molecules into these macromolecular complexes has important functional consequences for the cell; such as [[Membrane transport|ion and metabolite transport]], signaling, [[cell adhesion]], and [[Cell migration|migration]].<ref name="Nicolson2014"/>
 
===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 [[Cellular compartment|compartmentalization]]. Moreover, they impose physical constraints that restrict the free lateral diffusion of proteins and at least some lipids within the bilipid layer.<ref name="Nicolson2014"/>
 
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.<ref>{{cite journal | vauthors = Vereb G, Szöllosi J, Matkó J, Nagy P, Farkas T, Vigh L, Mátyus L, Waldmann TA, Damjanovich S | display-authors = 6 | title = Dynamic, yet structured: The cell membrane three decades after the Singer-Nicolson model | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 14 | pages = 8053–8058 | date = July 2003 | pmid = 12832616 | pmc = 166180 | doi = 10.1073/pnas.1332550100 | doi-access = free | bibcode = 2003PNAS..100.8053V }}</ref> Both processes restrict the diffusion of proteins and lipids directly involved, as well as of other interacting components of the cell membranes.
 
[[File:S cerevisiae septins.jpg|thumb|alt=alt text|''S.cerevisiae'' septins<br>Septin ring-like structures (in green) can pinch cell membranes and split them into subdomains.]]

[[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.<ref>{{cite journal | vauthors = Saarikangas J, Barral Y | title = The emerging functions of septins in metazoans | journal = EMBO Reports | volume = 12 | issue = 11 | pages = 1118–1126 | date = October 2011 | pmid = 21997296 | pmc = 3207108 | doi = 10.1038/embor.2011.193 }}</ref>

==Historical timeline==

* '''1895''' – [[Ernest Overton]] hypothesized that cell membranes are made out of lipids.<ref>{{cite journal | vauthors = Overton E |title=Uberdie osmotischen Eigenshafter der Lebenden Pflanzen und tierzelle |journal=VJSCHR Naturf Ges Zurich |volume=40 |pages=159–201 |date=1895|url=https://archive.org/details/ueberdieosmotis00overgoog}}</ref>
* '''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.<ref>{{cite journal | vauthors = Gorter E, Grendel F | title = On Bimolecular Layers of Lipoids on the Chromocytes of the Blood | journal = The Journal of Experimental Medicine | volume = 41 | issue = 4 | pages = 439–443 | date = March 1925 | pmid = 19868999 | pmc = 2130960 | doi = 10.1084/jem.41.4.439 }}</ref>
* '''1935''' – [[Hugh Davson]] and [[James Danielli]]  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.<ref>{{cite journal | vauthors = Danielli J, Davson H |title=A contribution to the theory of permeability of thin films |journal=Journal of Cellular and Comparative Physiology|volume=5 |issue=4 |pages=495–508 |date=1935 |doi=10.1002/jcp.1030050409}}</ref>
* '''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.<ref>{{cite journal |vauthors=Heuser JE |title=In Memory of J. David Robertson |journal=Newsletter of the American Society of Cell Biology |date=1995 |url=http://www.heuserlab.wustl.edu/experience/Robertson%20obit.pdf |access-date=2014-12-05 |archive-date=2018-10-08 |archive-url=https://web.archive.org/web/20181008055202/http://www.heuserlab.wustl.edu/experience/Robertson%20obit.pdf |url-status=dead }}</ref>
* '''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.<ref name="Singer1972"/>
* '''1997''' – K Simons and E Ikonen proposed the lipid raft theory as an initial explanation of membrane zonation.<ref>{{cite journal |last1=Simons |first1=Kai |last2=Ikonen |first2=Elina |title=Functional rafts in cell membranes |url=https://www.nature.com/articles/42408 |journal=Nature |pages=569–572 |language=en |doi=10.1038/42408 |date=June 1997|volume=387 |issue=6633 |pmid=9177342 |bibcode=1997Natur.387..569S |url-access=subscription }}</ref>
* '''2024''' – TA Kervin and M Overduin proposed the proteolipid code to fully explain membrane zonation as the lipid raft theory became increasingly controversial.<ref>{{cite journal |last1=Kervin |first1=Troy A. |last2=Overduin |first2=Michael |title=Membranes are functionalized by a proteolipid code |journal=BMC Biology |pages=46 |doi=10.1186/s12915-024-01849-6 |date=27 February 2024|volume=22 |issue=1 |doi-access=free |pmid=38414038 |pmc=10898092 }}</ref><ref>{{cite journal |last1=Leslie |first1=Mitch |title=Do Lipid Rafts Exist? |url=https://www.science.org/doi/10.1126/science.334.6059.1046-b |journal=Science |pages=1046–1047 |language=en |doi=10.1126/science.334.6059.1046-b |date=25 November 2011|volume=334 |issue=6059 |pmid=22116853 |bibcode=2011Sci...334.1046L |url-access=subscription }}</ref>

==Notes and references==
{{Reflist|2}}

{{Organelles}}
{{Structures of the cell membrane}}

{{DEFAULTSORT:Fluid mosaic}}
[[Category:Membrane biology]]
[[Category:Organelles]]
[[Category:Cell anatomy]]