Editing Lipid bilayer (section)

===Asymmetry===
In many naturally occurring bilayers, the compositions of the inner and outer membrane leaflets are different. In human [[erythrocyte|red blood cells]], the inner (cytoplasmic) leaflet is composed mostly of [[phosphatidylethanolamine]], [[phosphatidylserine]] and [[phosphatidylinositol]] and its phosphorylated derivatives. By contrast, the outer (extracellular) leaflet is based on [[phosphatidylcholine]], [[sphingomyelin]] and a variety of glycolipids.<ref name=Bretscher1972>{{cite journal|title=Asymmetrical Lipid Bilayer Structure for Biological Membranes|journal=Nature New Biology|date=1 March 1972|volume=236|issue=61|pages=11–12|doi=10.1038/newbio236011a0|pmid=4502419 |author=Bretscher MS }}</ref><ref name=Verkleij1973>{{cite journal |vauthors=Verkleij AJ, Zwaal RF, Roelofsen B, Comfurius P, Kastelijn D, van Deenen LL |title=The asymmetric distribution of phospholipids in the human red cell membrane. A combined study using phospholipases and freeze-etch electron microscopy |journal=Biochim. Biophys. Acta |volume=323 |issue=2 |pages=178–93 |date=October 1973 |pmid=4356540 |doi=10.1016/0005-2736(73)90143-0}}</ref><ref>{{Cite journal|last1=Coones|first1=R. T.|last2=Green|first2=R. J.|last3=Frazier|first3=R. A.|date=2021|title=Investigating lipid headgroup composition within epithelial membranes: a systematic review|url=http://xlink.rsc.org/?DOI=D1SM00703C|journal=Soft Matter|language=en|volume=17|issue=28|pages=6773–6786|doi=10.1039/D1SM00703C|pmid=34212942|bibcode=2021SMat...17.6773C|s2cid=235708094|issn=1744-683X|doi-access=free}}</ref> In some cases, this asymmetry is based on where the lipids are made in the cell and reflects their initial orientation.<ref name=Bell1981>{{cite journal |vauthors=Bell RM, Ballas LM, Coleman RA |title=Lipid topogenesis |journal=J. Lipid Res. |volume=22 |issue=3 |pages=391–403 |date=1 March 1981|doi=10.1016/S0022-2275(20)34952-X |pmid=7017050 |url=http://www.jlr.org/cgi/pmidlookup?view=long&pmid=7017050 |doi-access=free }}</ref> The biological functions of lipid asymmetry are imperfectly understood, although it is clear that it is used in several different situations. For example, when a cell undergoes [[apoptosis]], the phosphatidylserine&nbsp;— normally localised to the cytoplasmic leaflet&nbsp;— is transferred to the outer surface: There, it is recognised by a [[macrophage]] that then actively scavenges the dying cell.<ref name=Fadoka1998/>

Lipid asymmetry arises, at least in part, from the fact that most phospholipids are synthesised and initially inserted into the inner monolayer: those that constitute the outer monolayer are then transported from the inner monolayer by a class of enzymes called [[flippase]]s.<ref name=Bretscher1973>{{cite journal |doi=10.1126/science.181.4100.622 |author=Bretscher MS |title=Membrane structure: some general principles |journal=Science |volume=181 |issue=4100 |pages=622–629 |date=August 1973 |pmid=4724478 |bibcode=1973Sci...181..622B |s2cid=34501546 }}</ref><ref name=Rothman1977>{{cite journal |vauthors=Rothman JE, Kennedy EP |title=Rapid transmembrane movement of newly synthesized phospholipids during membrane assembly |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=74 |issue=5 |pages=1821–5 |date=May 1977 |pmid=405668 |pmc=431015 |doi=10.1073/pnas.74.5.1821 |bibcode=1977PNAS...74.1821R |doi-access=free }}</ref> Other lipids, such as sphingomyelin, appear to be synthesised at the external leaflet. Flippases are members of a larger family of lipid transport molecules that also includes floppases, which transfer lipids in the opposite direction, and scramblases, which randomize lipid distribution across lipid bilayers (as in apoptotic cells). In any case, once lipid asymmetry is established, it does not normally dissipate quickly because spontaneous flip-flop of lipids between leaflets is extremely slow.<ref name=Kornberg1971>{{cite journal |vauthors=Kornberg RD, McConnell HM |title=Inside-outside transitions of phospholipids in vesicle membranes |journal=Biochemistry |volume=10 |issue=7 |pages=1111–20 |date=March 1971 |pmid=4324203 |doi=10.1021/bi00783a003 }}</ref>

It is possible to mimic this asymmetry in the laboratory in model bilayer systems. Certain types of very small artificial [[Vesicle (biology)|vesicle]] will automatically make themselves slightly asymmetric, although the mechanism by which this asymmetry is generated is very different from that in cells.<ref name=Litman1974>{{cite journal |author=Litman BJ |title=Determination of molecular asymmetry in the phosphatidylethanolamine surface distribution in mixed phospholipid vesicles |journal=Biochemistry |volume=13 |issue=14 |pages=2844–8 |date=July 1974 |pmid=4407872 |doi=10.1021/bi00711a010 }}</ref> By utilizing two different monolayers in [[Langmuir-Blodgett film|Langmuir-Blodgett]] deposition<ref name=Crane2005>{{cite journal |vauthors=Crane JM, Kiessling V, Tamm LK |title=Measuring lipid asymmetry in planar supported bilayers by fluorescence interference contrast microscopy |journal=Langmuir |volume=21 |issue=4 |pages=1377–88 |date=February 2005 |pmid=15697284 |doi=10.1021/la047654w }}</ref> or a combination of Langmuir-Blodgett and vesicle rupture deposition<ref name=Kalb1992>{{cite journal |vauthors=Kalb E, Frey S, Tamm LK |title=Formation of supported planar bilayers by fusion of vesicles to supported phospholipid monolayers |journal=Biochim. Biophys. Acta |volume=1103 |issue=2 |pages=307–16 |date=January 1992 |pmid=1311950 |doi=10.1016/0005-2736(92)90101-Q}}</ref> it is also possible to synthesize an asymmetric planar bilayer. This asymmetry may be lost over time as lipids in supported bilayers can be prone to flip-flop.<ref name=Lin2006>{{cite journal |vauthors=Lin WC, Blanchette CD, Ratto TV, Longo ML |title=Lipid asymmetry in DLPC/DSPC-supported lipid bilayers: a combined AFM and fluorescence microscopy study |journal=Biophys. J. |volume=90 |issue=1 |pages=228–37 |date=January 2006 |pmid=16214871 |pmc=1367021 |doi=10.1529/biophysj.105.067066 |bibcode=2006BpJ....90..228L }}</ref> However, it has been reported that lipid flip-flop is slow compare to cholesterol and other smaller molecules.<ref>{{Cite journal |last1=Perez-Salas |first1=Ursula |last2=Porcar |first2=Lionel |last3=Garg |first3=Sumit |last4=Ayee |first4=Manuela A. A. |last5=Levitan |first5=Irena |date=October 2022 |title=Effective Parameters Controlling Sterol Transfer: A Time-Resolved Small-Angle Neutron Scattering Study |url=https://pubmed.ncbi.nlm.nih.gov/35467109/ |journal=The Journal of Membrane Biology |volume=255 |issue=4–5 |pages=423–435 |doi=10.1007/s00232-022-00231-3 |issn=1432-1424 |pmid=35467109|s2cid=248375027 }}</ref><ref>{{Cite journal |last1=Garg |first1=S. |last2=Porcar |first2=L. |last3=Woodka |first3=A. C. |last4=Butler |first4=P. D. |last5=Perez-Salas |first5=U. |date=2011-07-20 |title=Noninvasive neutron scattering measurements reveal slower cholesterol transport in model lipid membranes |journal=Biophysical Journal |volume=101 |issue=2 |pages=370–377 |doi=10.1016/j.bpj.2011.06.014 |issn=1542-0086 |pmc=3136766 |pmid=21767489|bibcode=2011BpJ...101..370G }}</ref>

It has been reported that the organization and dynamics of the lipid monolayers in a bilayer are coupled.<ref name=":0">{{Cite journal |last1=Deverall |first1=Miranda A. |last2=Garg |first2=Sumit |last3=Lüdtke |first3=Karin |last4=Jordan |first4=Rainer |last5=Rühe |first5=Jürgen |last6=Naumann |first6=Christoph A. |date=2008-08-12 |title=Transbilayer coupling of obstructed lipid diffusion in polymer-tethered phospholipid bilayers |url=https://pubs.rsc.org/en/content/articlelanding/2008/sm/b800801a |journal=Soft Matter |language=en |volume=4 |issue=9 |pages=1899–1908 |doi=10.1039/B800801A |bibcode=2008SMat....4.1899D |issn=1744-6848}}</ref><ref name=":1">{{Cite journal |last1=Garg |first1=Sumit |last2=Rühe |first2=Jürgen |last3=Lüdtke |first3=Karin |last4=Jordan |first4=Rainer |last5=Naumann |first5=Christoph A. |date=2007-02-15 |title=Domain Registration in Raft-Mimicking Lipid Mixtures Studied Using Polymer-Tethered Lipid Bilayers |journal=Biophysical Journal |language=en |volume=92 |issue=4 |pages=1263–1270 |doi=10.1529/biophysj.106.091082 |pmid=17114215 |pmc=1783876 |bibcode=2007BpJ....92.1263G |issn=0006-3495}}</ref> For example, introduction of obstructions in one monolayer can slow down the lateral diffusion in both monolayers.<ref name=":0" /> In addition, phase separation in one monolayer can also induce phase separation in other monolayer even when other monolayer can not phase separate by itself.<ref name=":1" />