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| {{see also|Model lipid bilayer}}
| | If the vaccine only works for five years, is administered up to age 26, and yet most cases of cervical cancer happen to women in their 50s, the benefits of the Gardasil vaccine are questionable given the severe consequences it can cause. Across the London, this fabulous salon is famous by the name of. Generally the greatest number of these use herbs and other natural healing methods to cure someone of their genital warts. It does not immediately attack the human papilloma virus, but directs body's immune to make the warts less visible due to which they eventually go away. There are more than 100 different types of HPV, but only a few can cause genital warts. <br><br>People suffering from genital warts suffer from depression and frustration. So, naturally people will be curious about possible ways how to get rid of genital warts. Some of the medications help in removing the warts from the surface of the skin. At the number two spot is Healing Natural Oils Heal Warts. It doesn’t necessarily mean that coming into contact with a contagious person that you will contract the virus, it all depends on the type of wart and the health and condition of your skin on whether you’ll contract the virus from touching someone else’s wart. <br><br>Some treatments include laser surgical procedure or applying some chemical solutions on the infected area. Researchers also noted that vaccinated men in their 20s may be too late. Some of these genital warts are found in the vaginal walls and could clearly be thought to be a yeast infection. FOR MORE INFO: Contact the Centers for Disease Control. Warts on the your body parts is usually painful and also disturbing. <br><br>In addition to burning and freezing off the warts, they can also be surgically removed by cutting them off the skin. The most common STD complications are malignancy, chronic pain, sterility, skin problem and even loss of sight. Repeat this particular approach daily until the warts are healed. Maintaining a healthy lifestyle will decrease the chances of recurrences, and in time, most people stop having any recurrences. Feeling very painful during intercourse could be a symptom of genital warts. <br><br>Most of the time the virus will clear up on its own. Another medication that can be used to fight the warts is podofilox(Condylox) and podophyllin. DO NOT treat warts on your face or genitals yourself. Electric current can also be utilized to burn up the actual warts and is known as Electrosurgery. This cream is a medication that is often recommended for long term use. <br><br>Skin Tags may be raised or flat, small or massive, single or multiple; often they appear pinkish or flesh-colored moist, comfortable swellings. Few drops of apple cider vinegar on a cotton ball if massaged gently on the infected areas cures genital warts. Pathogens are tiny; a microscope is needed to see them. Do not know what would happen if fear keeps minds doni coupled with agonizing disease. The virus that causes genital warts can remain within you for several years and produce an outbreak of warts at any time.<br><br>When you loved this informative article and you would want to receive details concerning [http://www.molesandwarts.info/ hpv wart removal] kindly visit the page. |
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| [[Image:Lipid bilayer section.gif|right|thumb|300px|This fluid [[lipid]] bilayer cross section is made up entirely of [[phosphatidylcholine]].]]
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| The '''lipid bilayer''' is a thin [[polar membrane]] made of two layers of [[lipid]] [[molecule]]s. These membranes are flat sheets that form a continuous barrier around [[cell (biology)|cells]]. The [[cell membrane]] of almost all [[life|living organisms]] and many [[virus]]es are made of a lipid bilayer, as are the membranes surrounding the [[cell nucleus]] and other sub-cellular structures. The lipid bilayer is the barrier that keeps [[ion]]s, [[protein]]s and other molecules where they are needed and prevents them from diffusing into areas where they should not be. Lipid bilayers are ideally suited to this role because, even though they are only a few [[nanometer]]s in width, they are impermeable to most water-soluble ([[hydrophilic]]) molecules. Bilayers are particularly impermeable to ions, which allows cells to regulate salt concentrations and [[pH]] by pumping ions across their membranes using proteins called [[Ion transporter|ion pumps]].
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| Natural bilayers are usually composed of [[phospholipid]]s, which have a hydrophilic head and two [[hydrophobic]] tails each. When phospholipids are exposed to water, they arrange themselves into a two-layered sheet (a bilayer) with all of their tails pointing toward the center of the sheet. The center of this bilayer contains almost no water and excludes molecules like [[sugar]]s or salts that dissolve in water but not in oil. This assembly process is similar to the coalescing of oil droplets in water and is driven by the same force, called the [[hydrophobic effect]]. Because lipid bilayers are quite fragile and are so thin that they are invisible in a traditional microscope, bilayers are very challenging to study. Experiments on bilayers often require advanced techniques like [[electron microscopy]] and [[atomic force microscopy]].
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| Phospholipids with certain head groups can alter the surface chemistry of a bilayer and can, for example, mark a cell for destruction by the [[immune system]]. Lipid tails can also affect membrane properties, for instance by determining the [[Phase (matter)|phase]] of the bilayer. The bilayer can adopt a solid [[gel]] phase state at lower temperatures but undergo [[phase transition]] to a [[Fluids|fluid state]] at higher temperatures. The packing of lipids within the bilayer also affects its mechanical properties, including its resistance to stretching and bending. Many of these properties have been studied with the use of artificial "model" bilayers produced in a lab. [[Vesicle (biology)|Vesicles]] made by model bilayers have also been used clinically to deliver drugs.
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| [[Biological membrane]]s typically include several types of lipids other than phospholipids. A particularly important example in animal cells is [[cholesterol]], which helps strengthen the bilayer and decrease its permeability. Cholesterol also helps regulate the activity of certain [[integral membrane protein]]s. Integral membrane proteins function when incorporated into a lipid bilayer. Because bilayers define the boundaries of the cell and its compartments, these membrane proteins are involved in many intra- and inter-cellular signaling processes. Certain kinds of membrane proteins are involved in the process of fusing two bilayers together. This fusion allows the joining of two distinct structures as in the [[fertilization]] of an [[egg (biology)|egg]] by [[sperm]] or the entry of a [[virus]] into a cell.
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| [[File:Phospholipids aqueous solution structures.svg|thumb|right|300px|The three main structures phospholipids form in solution; the [[liposome]] (a closed bilayer), the micelle and the bilayer.]]
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| ==Structure and organization==
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| A lipid bilayer, also known as the phospholipid bilayer, is a sheet of [[lipid]]s two molecules thick, arranged so that the [[hydrophilic]] phosphate heads point “out” to the water on either side of the bilayer and the [[hydrophobic]] tails point “in” to the core of the bilayer. This arrangement results in two “leaflets” which are each a single molecular layer. Lipids self-assemble into this structure because of the [[hydrophobic effect]] which creates an energetically unfavorable interaction between the hydrophobic lipid tails and the surrounding water. Thus, a lipid bilayer is typically held together by entirely [[Noncovalent bonding|non-covalent forces]] that do not involve formation of chemical bonds between individual molecules.
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| There are a few similarities between this structure and a common [[soap bubble]], although there are also important differences. As illustrated, both structures involve two single-molecule layers of an [[amphiphilic]] substance. In the case of a soap bubble, the two soap monolayers coat an intervening water layer. The hydrophilic heads are oriented “in” toward this water core, while the hydrophobic tails point “out” to the air. In the case of a lipid bilayer, this structure is reversed with heads out and tails in. Another important difference between lipid bilayers and soap bubbles is their relative size. Soap bubbles are typically hundreds of nanometers thick, on the same order as the wavelength of light, which is why [[Interference (wave propagation)|interference]] effects cause rainbow colors on a bubble surface. A single lipid bilayer, on the other hand, is around five nanometers thick, much smaller than the wavelength of light and is therefore invisible to the eye, even with a standard light microscope.
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| [[Image:Bilayer hydration profile.svg|left|thumb|310px| Schematic cross sectional profile of a typical lipid bilayer. There are three distinct regions: the fully hydrated headgroups, the fully dehydrated alkane core and a short intermediate region with partial hydration. Although the head groups are neutral, they have significant dipole moments which influence the molecular arrangement.<ref>Mashaghi et al. Hydration strongly affects the molecular and electronic structure of membrane phospholipids. 136, 114709 (2012)[http://jcp.aip.org/resource/1/jcpsa6/v136/i11/p114709_s1]</ref>]]
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| ===Cross section analysis===
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| The lipid bilayer is very thin compared to its lateral dimensions. If a typical mammalian cell (diameter ~10 micrometre) were magnified to the size of a watermelon (~1 ft/30 cm), the lipid bilayer making up the [[plasma membrane]] would be about as thick as a piece of office paper. Despite being only a few nanometers thick, the bilayer is composed of several distinct chemical regions across its cross-section. These regions and their interactions with the surrounding water have been characterized over the past several decades with [[x-ray reflectometry]],<ref name=Lewis1983>{{cite journal |author=Lewis BA, Engelman DM |title=Lipid bilayer thickness varies linearly with acyl chain length in fluid phosphatidylcholine vesicles |journal=J. Mol. Biol. |volume=166 |issue=2 |pages=211–7 |date=May 1983 |pmid=6854644 |doi=10.1016/S0022-2836(83)80007-2 }}</ref> [[neutron scattering]]<ref name=Zaccai1975>{{cite journal |author=Zaccai G, Blasie JK, Schoenborn BP |title=Neutron Diffraction Studies on the Location of Water in Lecithin Bilayer Model Membranes |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=72 |issue=1 |pages=376–380 |date=January 1975 |pmid=16592215 |pmc=432308 |doi=10.1073/pnas.72.1.376 |bibcode = 1975PNAS...72..376Z }}</ref> and [[nuclear magnetic resonance]] techniques.
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| The first region on either side of the bilayer is the hydrophilic headgroup. This portion of the membrane is completely hydrated and is typically around 0.8-0.9 nm thick. In [[phospholipid]] bilayers the [[phosphate]] group is located within this hydrated region, approximately 0.5 nm outside the hydrophobic core.<ref name=Nagle2000>{{cite journal |author=Nagle JF, Tristram-Nagle S |title=Structure of lipid bilayers |journal=Biochim. Biophys. Acta |volume=1469 |issue=3 |pages=159–95 |date=November 2000 |pmid=11063882 |url=http://linkinghub.elsevier.com/retrieve/pii/S0304-4157(00)00016-2 |pmc=2747654 |doi=10.1016/S0304-4157(00)00016-2}}</ref> In some cases, the hydrated region can extend much further, for instance in lipids with a large protein or long sugar chain grafted to the head. One common example of such a modification in nature is the [[lipopolysaccharide]] coat on a bacterial outer membrane,<ref name=Brock2003>{{cite book |author=Parker J, Madigan MT, Brock TD, Martinko JM |title=Brock biology of microorganisms |publisher=Prentice Hall |location=Englewood Cliffs, N.J |year=2003 |edition=10th |isbn=0-13-049147-0 }}</ref> which helps retain a water layer around the [[bacterium]] to prevent dehydration.
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| [[Image:Bacillus subtilis.jpg|right|thumb|240px| [[Transmission electron microscopy|TEM]] image of a bacterium. The furry appearance on the outside is due to a coat of long chain sugars attached to the cell membrane. This coating helps trap water to prevent the bacterium from becoming dehydrated.]]
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| Next to the hydrated region is an intermediate region which is only partially hydrated. This boundary layer is approximately 0.3 nm thick. Within this short distance, the water concentration drops from 2M on the headgroup side to nearly zero on the tail (core) side.<ref name=Marsh2001>{{cite journal |author=Marsh D |title=Polarity and permeation profiles in lipid membranes |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue=14 |pages=7777–82 |date=July 2001 |pmid=11438731 |pmc=35418 |doi=10.1073/pnas.131023798 |bibcode = 2001PNAS...98.7777M }}</ref><ref name=Marsh2002>{{cite journal |author=Marsh D |title=Membrane water-penetration profiles from spin labels |journal=Eur. Biophys. J. |volume=31 |issue=7 |pages=559–62 |date=December 2002 |pmid=12602343 |doi=10.1007/s00249-002-0245-z }}</ref> The hydrophobic core of the bilayer is typically 3-4 nm thick, but this value varies with chain length and chemistry.<ref name=Lewis1983/><ref name=Rawicz2000>{{cite journal |author=Rawicz W, Olbrich KC, McIntosh T, Needham D, Evans E |title=Effect of chain length and unsaturation on elasticity of lipid bilayers |journal=Biophys. J. |volume=79 |issue=1 |pages=328–39 |date=July 2000 |pmid=10866959 |pmc=1300937 |doi=10.1016/S0006-3495(00)76295-3 |bibcode=2000BpJ....79..328R}}</ref> Core thickness also varies significantly with temperature, particularly near a phase transition.<ref name=Trauble1971>{{cite journal |author=Trauble H, Haynes DH |title=The volume change in lipid bilayer lamellae at the crystalline-liquid crystalline phase transition |journal=Chem. Phys. Lipids. |volume=7 |issue=4 |pages=324–35 |year=1971 |doi=10.1016/0009-3084(71)90010-7}}</ref>
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| ===Asymmetry===
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| 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 largely composed 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 |doi=10.1038/236011a0 |author=Bretscher MS, |title= Asymmetrical lipid bilayer structure for biological membranes |journal=Nature |volume=236 |issue=61 |pages=11–12 |date=March 1972 |pmid=4502419|bibcode = 1972Natur.236...11O }}</ref><ref name=Verkleij1973>{{cite journal |author=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 |url=http://linkinghub.elsevier.com/retrieve/pii/0005-2736(73)90143-0 |doi=10.1016/0005-2736(73)90143-0}}</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 |author=Bell RM, Ballas LM, Coleman RA |title=Lipid topogenesis |journal=J. Lipid Res. |volume=22 |issue=3 |pages=391–403 |date=1 March 1981|pmid=7017050 |url=http://www.jlr.org/cgi/pmidlookup?view=long&pmid=7017050 }}</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 — normally localised to the cytoplasmic leaflet — is transferred to the outer surface: there it is recognised by a [[macrophage]] which then actively scavenges the dying cell.
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| 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 }}</ref><ref name=Rothman1977>{{cite journal |author=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 }}</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 which 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 |author=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>
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| 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 |author=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 |author=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 |url=http://linkinghub.elsevier.com/retrieve/pii/0005-2736(92)90101-Q |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 |author=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>
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| ===Phases and phase transitions===
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| [[Image:Lipid unsaturation effect.svg|right|thumb|350px|Diagram showing the effect of unsaturated lipids on a bilayer. The lipids with an unsaturated tail (blue) disrupt the packing of those with only saturated tails (black). The resulting bilayer has more free space and is consequently more permeable to water and other small molecules.]]
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| {{further2|[[Lipid bilayer phase behavior]]}}
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| At a given temperature a lipid bilayer can exist in either a liquid or a gel (solid) phase. All lipids have a characteristic temperature at which they transition (melt) from the gel to liquid phase. In both phases the lipid molecules are prevented from flip-flopping across the bilayer, but in liquid phase bilayers a given lipid will exchange locations with its neighbor millions of times a second. This [[random walk]] exchange allows lipid to [[diffusion|diffuse]] and thus wander across the surface of the membrane.<ref name=Berg1993>{{cite book |author=Berg, Howard C. |title=Random walks in biology |publisher=Princeton University Press |location=Princeton, N.J |year=1993 |isbn=0-691-00064-6 |edition=Extended Paperback}}</ref> Unlike liquid phase bilayers, the lipids in a gel phase bilayer are locked in place.
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| The phase behavior of lipid bilayers is largely determined by the strength of the attractive [[van der Waals force|Van der Waals]] interactions between adjacent lipid molecules. Longer tailed lipids have more area over which to interact, increasing the strength of this interaction and consequently decreasing the lipid mobility. Thus, at a given temperature, a short-tailed lipid will be more fluid than an otherwise identical long-tailed lipid.<ref name=Rawicz2000/> Transition temperature can also be affected by the [[degree of unsaturation]] of the lipid tails. An unsaturated [[double bond]] can produce a kink in the [[alkane]] chain, disrupting the lipid packing. This disruption creates extra free space within the bilayer which allows additional flexibility in the adjacent chains.<ref name=Rawicz2000/> An example of this effect can be noted in everyday life as butter, which has a large percentage saturated fats, is solid at room temperature while vegetable oil, which is mostly unsaturated, is liquid.
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| Most natural membranes are a complex mixture of different lipid molecules. If some of the components are liquid at a given temperature while others are in the gel phase, the two phases can coexist in spatially separated regions, rather like an iceberg floating in the ocean. This phase separation plays a critical role in biochemical phenomena because membrane components such as proteins can partition into one or the other phase<ref name=Dietrich2001>{{cite journal |author=Dietrich C, Volovyk ZN, Levi M, Thompson NL, Jacobson K |title=Partitioning of Thy-1, GM1, and cross-linked phospholipid analogs into lipid rafts reconstituted in supported model membrane monolayers |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue=19 |pages=10642–7 |date=September 2001 |pmid=11535814 |pmc=58519 |doi=10.1073/pnas.191168698 |bibcode = 2001PNAS...9810642D }}</ref> and thus be locally concentrated or activated. One particularly important component of many mixed phase systems is [[cholesterol]], which modulates bilayer permeability, mechanical strength and biochemical interactions.
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| ===Surface chemistry===
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| While lipid tails primarily modulate bilayer phase behavior, it is the headgroup that determines the bilayer surface chemistry. Most natural bilayers are composed primarily of [[phospholipid]]s, although sphingolipids such as [[sphingomyelin]] and [[sterol]]s such as [[cholesterol]] are also important components. Of the phospholipids, the most common headgroup is [[phosphatidylcholine]] (PC), accounting for about half the phospholipids in most mammalian cells.<ref name=Yeagle1993/> PC is a [[Zwitterion|zwitterionic]] headgroup, as it has a negative charge on the phosphate group and a positive charge on the amine but, because these local charges balance, no net charge.
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| Other headgroups are also present to varying degrees and can include [[phosphatidylserine]] (PS) [[phosphatidylethanolamine]] (PE) and [[phosphatidylglycerol]] (PG). These alternate headgroups often confer specific biological functionality that is highly context-dependent. For instance, PS presence on the extracellular membrane face of [[erythrocyte]]s is a marker of cell [[apoptosis]],<ref name=Fadoka1998>{{cite journal |author=Fadok VA, Bratton DL, Frasch SC, Warner ML, Henson PM |title=The role of phosphatidylserine in recognition of apoptotic cells by phagocytes |journal=Cell Death Differ. |volume=5 |issue=7 |pages=551–62 |date=July 1998 |pmid=10200509 |doi=10.1038/sj.cdd.4400404 }}</ref> whereas PS in [[growth plate]] vesicles is necessary for the [[nucleation]] of [[hydroxyapatite]] crystals and subsequent bone mineralization.<ref name=Anderson2005>{{cite journal |author=Anderson HC, Garimella R, Tague SE |title=The role of matrix vesicles in growth plate development and biomineralization |journal=Front. Biosci. |volume=10 |issue= 1–3|pages=822–37 |date=January 2005 |pmid=15569622 |url=http://www.bioscience.org/2005/v10/af/1576/fulltext.htm |doi=10.2741/1576}}</ref><ref name=Eanes1987>{{cite journal |author=Eanes ED, Hailer AW |title=Calcium phosphate precipitation in aqueous suspensions of phosphatidylserine-containing anionic liposomes |journal=Calcif. Tissue Int. |volume=40 |issue=1 |pages=43–8 |date=January 1987 |pmid=3103899 |doi=10.1007/BF02555727 }}</ref> Unlike PC, some of the other headgroups carry a net charge, which can alter the electrostatic interactions of small molecules with the bilayer.<ref name=Kim1991>{{cite journal |author=Kim J, Mosior M, Chung LA, Wu H, McLaughlin S |title=Binding of peptides with basic residues to membranes containing acidic phospholipids |journal=Biophys. J. |volume=60 |issue=1 |pages=135–48 |date=July 1991 |pmid=1883932 |pmc=1260045 |doi=10.1016/S0006-3495(91)82037-9 |bibcode=1991BpJ....60..135K}}</ref>
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| ==Biological roles==
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| ===Containment and separation===
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| The primary role of the lipid bilayer in biology is to separate [[Aqueous solution|aqueous]] compartments from their surroundings. Without some form of barrier delineating “self” from “non-self” it is difficult to even define the concept of an organism or of life. This barrier takes the form of a lipid bilayer in all known life forms except for a few species of [[archaea]] which utilize a specially adapted lipid monolayer.<ref name=Brock2003/> It has even been proposed that the very first form of life may have been a simple [[lipid vesicle]] with virtually its sole [[Biosynthesis|biosynthetic]] capability being the production of more [[phospholipid]]s.<ref name=Koch1985>{{cite journal |author=Koch AL |title=Primeval cells: possible energy-generating and cell-division mechanisms |journal=J. Mol. Evol. |volume=21 |issue=3 |pages=270–7 |year=1984 |pmid=6242168 |doi=10.1007/BF02102359 }}</ref> The partitioning ability of the lipid bilayer is based on the fact that [[hydrophilic]] molecules cannot easily cross the [[hydrophobic]] bilayer core, as discussed in Transport across the bilayer below. Nucleus, mitochondria and chloroplasts have two lipid bilayer, and other structures are surrounded by a single lipid bilayer (such as the plasma membrane, endoplasmic reticula, Golgi apparatuses and lysosomes). See [[Organelle]].<ref>http://csls-text.c.u-tokyo.ac.jp/active/05_01.html</ref>
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| [[Prokaryote]]s have only one lipid bilayer- the [[cell membrane]] (also known as the plasma membrane). Many prokaryotes also have a [[cell wall]], but the cell wall is composed of [[protein]]s or long chain [[carbohydrate]]s, not lipids. In contrast, [[eukaryote]]s have a range of [[organelle]]s including the [[Cell nucleus|nucleus]], [[mitochondria]], [[lysosome]]s and [[endoplasmic reticulum]]. All of these sub-cellular compartments are surrounded by one or more lipid bilayers and, together, typically comprise the majority of the bilayer area present in the cell. In liver [[hepatocyte]]s for example, the plasma membrane accounts for only two percent of the total bilayer area of the cell, whereas the endoplasmic reticulum contains more than fifty percent and the mitochondria a further thirty percent.<ref name=Alberts2002/>
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| [[Image:7TM4 (GPCR).png|thumb|260px|Illustration of a GPCR signaling protein. In response to a molecule such as a [[hormone]] binding to the exterior domain (blue) the GPCR changes shape and [[catalyzes]] a chemical reaction on the interior domain (red). The gray feature is the surrounding bilayer.]]
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| ===Signaling===
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| {{see also|Neurotransmission|Lipid raft}}
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| Probably the most familiar form of cellular signaling is [[synaptic transmission]], whereby a nerve impulse that has reached the end of one [[neuron]] is conveyed to an adjacent neuron via the release of [[neurotransmitter]]s. This transmission is made possible by the action of [[synaptic vesicle]]s loaded with the neurotransmitters to be released. These vesicles [[Lipid bilayer fusion|fuse]] with the cell membrane at the pre-synaptic terminal and release its contents to the exterior of the cell. The contents then diffuse across the synapse to the post-synaptic terminal.
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| Lipid bilayers are also involved in signal transduction through their role as the home of [[integral membrane protein]]s. This is an extremely broad and important class of biomolecule. It is estimated that up to a third of the human [[proteome]] may be membrane proteins.<ref name=Martelli2003>{{cite journal |author=Martelli PL, Fariselli P, Casadio R |title=An ENSEMBLE machine learning approach for the prediction of all-alpha membrane proteins |journal=Bioinformatics |volume=19 |issue=Suppl 1|pages=i205–11 |year=2003 |pmid=12855459 |url=http://bioinformatics.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12855459 |doi=10.1093/bioinformatics/btg1027}}</ref> Some of these proteins are linked to the exterior of the cell membrane. An example of this is the [[CD59]] protein, which identifies cells as “self” and thus inhibits their destruction by the immune system. The [[HIV]] virus evades the [[immune system]] in part by grafting these proteins from the host membrane onto its own surface.<ref name=Alberts2002>{{cite book |author=Alberts, Bruce |title=Molecular biology of the cell |publisher=Garland Science |location=New York |year=2002 |edition=4th |isbn=0-8153-4072-9 }}</ref> Alternatively, some membrane proteins penetrate all the way through the bilayer and serve to relay individual signal events from the outside to the inside of the cell. The most common class of this type of protein is the [[G protein-coupled receptor]] (GPCR). GPCRs are responsible for much of the cell’s ability to sense its surroundings and, because of this important role, approximately 40% of all modern drugs are targeted at GPCRs.<ref name=Filmore2004>{{cite journal |author=Filmore D |title=It's A GPCR World |journal=Modern Drug Discovery |volume=11 |pages=24–9 |year=2004}}</ref>
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| In addition to protein- and solution-mediated processes, it is also possible for lipid bilayers to participate directly in signaling. A classic example of this is [[phosphatidylserine]]-triggered [[phagocytosis]]. Normally, phosphatidylserine is asymmetrically distributed in the cell membrane and is present only on the interior side. During programmed cell death a protein called a [[scramblase]] equilibrates this distribution, displaying phosphatidylserine on the extracellular bilayer face. The presence of phosphatidylserine then triggers phagocytosis to remove the dead or dying cell.
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| ==Characterization methods==
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| [[Image:Sedimented red blood cells.jpg|right|thumb|210px|Human red blood cells viewed through a fluorescence microscope. The [[cell membrane]] has been stained with a fluorescent dye. Scale bar is 20μm.]]
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| {{further2|[[Lipid bilayer characterization]]}}
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| [[Image:Annular Gap Junction Vesicle.jpg|left|thumb|220px| [[Transmission electron microscopy|Transmission Electron Microscope]] (TEM) image of a [[lipid vesicle]]. The two dark bands around the edge are the two leaflets of the bilayer. Historically, similar images confirmed that the cell membrane is a bilayer]]
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| The lipid bilayer is a very difficult structure to study because it is so thin and fragile. In spite of these limitations dozens of techniques have been developed over the last seventy years to allow investigations of its structure and function.
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| Electrical measurements are a straightforward way to characterize an important function of a bilayer: its ability to segregate and prevent the flow of ions in solution. By applying a voltage across the bilayer and measuring the resulting current, the [[Electrical resistance|resistance]] of the bilayer is determined. This resistance is typically quite high{{Citation needed|date=September 2011}} since the hydrophobic core is impermeable to charged species. The presence of even a few nanometer-scale holes results in a dramatic increase in current.<ref name=Melikov2001>{{cite journal |author=Melikov KC, Frolov VA, Shcherbakov A, Samsonov AV, Chizmadzhev YA, Chernomordik LV |title=Voltage-induced nonconductive pre-pores and metastable single pores in unmodified planar lipid bilayer |journal=Biophys. J. |volume=80 |issue=4 |pages=1829–36 |date=April 2001 |pmid=11259296 |pmc=1301372 |doi=10.1016/S0006-3495(01)76153-X |bibcode=2001BpJ....80.1829M}}</ref> The sensitivity of this system is such that even the activity of single [[ion channel]]s can be resolved.<ref name=Neher1976>{{cite journal |author=Neher E, Sakmann B |title=Single-channel currents recorded from membrane of denervated frog muscle fibres |journal=Nature |volume=260 |issue=5554 |pages=799–802 |date=April 1976 |pmid=1083489 |doi=10.1038/260799a0 |bibcode=1976Natur.260..799N}}</ref>
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| Electrical measurements do not provide an actual picture like imaging with a microscope can. Lipid bilayers cannot be seen in a traditional microscope because they are too thin. In order to see bilayers, researchers often use [[fluorescence microscopy]]. A sample is excited with one wavelength of light and observed in a different wavelength, so that only fluorescent molecules with a matching excitation and emission profile will be seen. Natural lipid bilayers are not fluorescent, so a dye is used that attaches to the desired molecules in the bilayer. Resolution is usually limited to a few hundred nanometers, much smaller than a typical cell but much larger than the thickness of a lipid bilayer.
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| [[Image:Supported Lipid Bilayer and Nanoparticles AFM.png|left|thumb|250px|3d-Adapted [[Atomic force microscope|AFM]] images showing formation of transmembrane pores (holes) in supported lipid bilayer <ref name=Lipid_and_nanoparticles/>]]
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| [[Image:Bilayer AFM schematic.png|right|thumb|250px|Illustration of a typical [[Atomic force microscopy|AFM]] scan of a supported lipid bilayer. The pits are defects in the bilayer, exposing the smooth surface of the substrate underneath.]]
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| [[Electron microscopy]] offers a higher resolution image. In an [[electron microscope]], a beam of focused [[electron]]s interacts with the sample rather than a beam of light as in traditional microscopy. In conjunction with rapid freezing techniques, electron microscopy has also been used to study the mechanisms of inter- and intracellular transport, for instance in demonstrating that [[Exocytosis|exocytotic]] vesicles are the means of chemical release at [[synapse]]s.<ref name=Heuser1979>{{cite journal |author=Heuser JE, Reese TS, Dennis MJ, Jan Y, Jan L, Evans L |title=Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release |journal=J. Cell Biol. |volume=81 |issue=2 |pages=275–300 |date=May 1979 |pmid=38256 |pmc=2110310 |url=http://www.jcb.org/cgi/pmidlookup?view=long&pmid=38256 |doi=10.1083/jcb.81.2.275}}</ref>
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| <sup>31</sup>P-NMR(nuclear magnetic resonance) spectroscopy is widely used for studies of phospholipid bilayers and biological membranes in native conditions. The analysis<ref name=Dubinnyi>{{cite journal |author=Dubinnyi MA, Lesovoy DM, Dubovskii PV, Chupin VV, Arseniev AS |title=Modeling of <sup>31</sup>P-NMR spectra of magnetically oriented phospholipid liposomes: A new analytical solution |journal=Solid State Nucl Magn Reson. |volume=29 |issue=4 |pages=305–311 |date=Jun 2006 |pmid=16298110 |url=http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6THK-4HKCYVB-1&_user=10&_coverDate=06%2F30%2F2006&_rdoc=9&_fmt=high&_orig=browse&_origin=browse&_zone=rslt_list_item&_srch=doc-info(%23toc%235285%232006%23999709995%23614865%23FLA%23display%23Volume)&_cdi=5285&_sort=d&_docanchor=&_ct=15&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=5d39b757c9976ffdf5d9318ae4e5f217&searchtype=a |doi=10.1016/j.ssnmr.2005.10.009}}</ref> of <sup>31</sup>P-NMR spectra of lipids could provide a wide range of information about lipid bilayer packing, phase transitions (gel phase, physiological liquid crystal phase, ripple phases, non bilayer phases), lipid head group orientation/dynamics, and elastic properties of pure lipid bilayer and as a result of binding of proteins and other biomolecules.
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| In addition, a specific H-N...(O)-P NMR experiment (INEPT transfer by scalar coupling 3JH-P~5 Hz) could provide a direct information about formation of hydrogen bonds between amid protons of protein to phosphate of lipid headgroups, which is useful in studies of protein/membrane interactions.
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| A new method to study lipid bilayers is [[Atomic force microscopy]] (AFM). Rather than using a beam of light or particles, a very small sharpened tip scans the surface by making physical contact with the bilayer and moving across it, like a record player needle. AFM is a promising technique because it has the potential to image with nanometer resolution at room temperature and even under water or physiological buffer, conditions necessary for natural bilayer behavior. Utilizing this capability, AFM has been used to examine dynamic bilayer behavior including the formation of transmembrane pores (holes)<ref name=Lipid_and_nanoparticles>Y. Roiter, M. Ornatska, A. R. Rammohan, J. Balakrishnan, D. R. Heine, and S. Minko, [http://dx.doi.org/10.1021/nl080080l Interaction of Nanoparticles with Lipid Membrane], Nano Letters, vol. 8, iss. 3, pp. 941–944 (2008).</ref> and phase transitions in supported bilayers.<ref name="Tokumasu et al. 2002">{{cite journal |author=Tokumasu F, Jin AJ, Dvorak JA |title=Lipid membrane phase behavior elucidated in real time by controlled environment atomic force microscopy |journal=J. Electron Micros. |volume=51 |issue=1 |pages=1–9 |year=2002 |doi=10.1093/jmicro/51.1.1 |pmid=12003236}}</ref> Another advantage is that AFM does not require fluorescent or [[isotope|isotopic]] labeling of the lipids, since the probe tip interacts mechanically with the bilayer surface. Because of this, the same scan can image both lipids and associated proteins, sometimes even with single-molecule resolution.<ref name=Lipid_and_nanoparticles/><ref name=Richter2003>{{cite journal |author=Richter RP, Brisson A |title=Characterization of lipid bilayers and protein assemblies supported on rough surfaces by atomic force microscopy |journal=Langmuir |volume=19 |issue=5 |pages=1632–40 |year=2003 |doi=10.1021/la026427w}}</ref> AFM can also probe the mechanical nature of lipid bilayers.<ref name=Steltenkamp2006>{{cite journal |author=Steltenkamp S, Müller MM, Deserno M, Hennesthal C, Steinem C, Janshoff A |title=Mechanical properties of pore-spanning lipid bilayers probed by atomic force microscopy |journal=Biophys. J. |volume=91 |issue=1 |pages=217–26 |date=July 2006 |pmid=16617084 |pmc=1479081 |doi=10.1529/biophysj.106.081398 |bibcode = 2006BpJ....91..217S }}</ref>
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| Lipid bilayers exhibit high levels of [[birefringence]] where the refractive index in the plane of the bilayer differs from that perpendicular by as much as 0.1 [[refractive index]] units. This has been used to characterise the degree of order and disruption in bilayers using [[dual polarisation interferometry]] to understand mechanisms of protein interaction.
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| Lipid bilayers are complicated molecular systems with many degrees of freedom. Thus atomistic simulation of membrane and in particular [[ab initio]] calculations of its properties is difficult and computationally expensive. Quantum chemical calculations has recently been successfully performed to estimate [[dipole]] and [[quadrupole]] moments of lipid membranes.<ref>Alireza Mashaghi et al., Hydration strongly affects the molecular and electronic structure of membrane phospholipids. J. Chem. Phys. 136, 114709 (2012) http://jcp.aip.org/resource/1/jcpsa6/v136/i11/p114709_s1</ref>
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| Hydrated bilayers show rich vibrational dynamics and are good media for efficient vibrational energy transfer. Vibrational properties of lipid monolayers and bilayers has been investigated by ultrafast spectroscopic techniques <ref>M. Bonn et al., Structural inhomogeneity of interfacial water at lipid monolayers revealed by surface-specific vibrational pump-probe spectroscopy, J. Am. Chem. Soc. 132, 14971–14978 (2010).</ref> and recently developed computational methods.<ref>Mischa Bonn et al., Interfacial Water Facilitates Energy Transfer by Inducing Extended Vibrations in Membrane Lipids, J Phys Chem, 2012 http://pubs.acs.org/doi/abs/10.1021/jp302478a</ref>
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| ==Transport across the bilayer==
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| ===Passive diffusion===
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| Most [[Chemical polarity|polar]] molecules have low solubility in the [[hydrocarbon]] core of a lipid bilayer and consequently have low permeability coefficients across the bilayer. This effect is particularly pronounced for charged species, which have even lower permeability coefficients than neutral polar molecules.<ref name=Chakrabarti1994>{{cite journal |author=Chakrabarti AC |title=Permeability of membranes to amino acids and modified amino acids: mechanisms involved in translocation |journal=Amino Acids |volume=6 |issue= 3|pages=213–29 |year=1994 |pmid=11543596 |doi=10.1007/BF00813743 }}</ref> [[Anion]]s typically have a higher rate of diffusion through bilayers than [[cation]]s.<ref name=Hauser1972>{{cite journal |author=Hauser H, Phillips MC, Stubbs M |title=Ion permeability of phospholipid bilayers |journal=Nature |volume=239 |issue=5371 |pages=342–4 |date=October 1972 |pmid=12635233 |doi=10.1038/239342a0 |bibcode = 1972Natur.239..342H }}</ref><ref name=Papahadjopoulos1967>{{cite journal |author=Papahadjopoulos D, Watkins JC |title=Phospholipid model membranes. II. Permeability properties of hydrated liquid crystals |journal=Biochim. Biophys. Acta |volume=135 |issue=4 |pages=639–52 |date=September 1967 |pmid=6048247 |url=http://linkinghub.elsevier.com/retrieve/pii/0005-2736(67)90095-8 |doi=10.1016/0005-2736(67)90095-8}}</ref> Compared to ions, water molecules actually have a relatively large permeability through the bilayer, as evidenced by [[Osmosis|osmotic swelling]]. When a cell or vesicle with a high interior salt concentration is placed in a solution with a low salt concentration it will swell and eventually burst. Such a result would not be observed unless water was able to pass through the bilayer with relative ease. The anomalously large permeability of water through bilayers is still not completely understood and continues to be the subject of active debate.<ref name=Paula1996>{{cite journal |author=Paula S, Volkov AG, Van Hoek AN, Haines TH, Deamer DW |title=Permeation of protons, potassium ions, and small polar molecules through phospholipid bilayers as a function of membrane thickness |journal=Biophys. J. |volume=70 |issue=1 |pages=339–48 |date=January 1996 |pmid=8770210 |pmc=1224932 |doi=10.1016/S0006-3495(96)79575-9 |bibcode=1996BpJ....70..339P}}</ref> Small uncharged apolar molecules diffuse through lipid bilayers many orders of magnitude faster than ions or water. This applies both to fats and organic solvents like [[chloroform]] and [[ether]]. Regardless of their polar character larger molecules diffuse more slowly across lipid bilayers than small molecules.<ref name=Xiang1994>{{cite journal |author=Xiang TX, Anderson BD |title=The relationship between permeant size and permeability in lipid bilayer membranes |journal=J. Membr. Biol. |volume=140 |issue=2 |pages=111–22 |date=June 1994 |pmid=7932645 }}</ref>
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| [[Image:1r3j.gif|left|thumb|250px|Structure of a potassium ion channel. The [[Alpha helix|alpha helices]] penetrate the bilayer (boundaries indicated by red and blue lines), opening a hole through which potassium ions can flow]]
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| ===Ion pumps and channels===
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| Two special classes of protein deal with the ionic gradients found across cellular and sub-cellular membranes in nature- [[ion channel]]s and [[Ion transporter|ion pumps]]. Both pumps and channels are [[integral membrane protein]]s that pass through the bilayer, but their roles are quite different. Ion pumps are the proteins that build and maintain the chemical gradients by utilizing an external energy source to move ions against the concentration gradient to an area of higher [[chemical potential]]. The energy source can be [[Adenosine triphosphate|ATP]], as is the case for the [[NaKATPase|Na<sup>+</sup>-K<sup>+</sup> ATPase]]. Alternatively, the energy source can be another chemical gradient already in place, as in the [[Sodium-calcium exchanger|Ca<sup>2+</sup>/Na<sup>+</sup> antiporter]]. It is through the action of ion pumps that cells are able to regulate [[pH]] via the [[Proton pump|pumping of protons]].
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| In contrast to ion pumps, ion channels do not build chemical gradients but rather dissipate them in order to perform work or send a signal. Probably the most familiar and best studied example is the [[Sodium channel|voltage-gated Na<sup>+</sup> channel]], which allows conduction of an [[action potential]] along [[neuron]]s. All ion pumps have some sort of trigger or “gating” mechanism. In the previous example it was electrical bias, but other channels can be activated by binding a molecular agonist or through a conformational change in another nearby protein.<ref name=Gouaux2005>{{cite journal |author=Gouaux E, Mackinnon R |title=Principles of selective ion transport in channels and pumps |journal=Science |volume=310 |issue=5753 |pages=1461–5 |date=December 2005 |pmid=16322449 |doi=10.1126/science.1113666 |bibcode = 2005Sci...310.1461G }}</ref>
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| [[Image:Pinocytosis.svg|right|210px|thumb|Schematic illustration of pinocytosis, a type of endocytosis]]
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| ===Endocytosis and exocytosis===
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| {{see also|Endocytosis|Exocytosis}}
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| Some molecules or particles are too large or too hydrophilic to effectively pass through a lipid bilayer. Other molecules could pass through the bilayer but must be transported rapidly in such large numbers that channel-type transport is impractical. In both cases these types of cargo can be moved across the cell membrane through [[Lipid bilayer fusion|fusion]] or budding of [[Lipid vesicle|vesicles]]. When a vesicle is produced inside the cell and fuses with the plasma membrane to release its contents into the extracellular space this process is known as exocytosis. In the reverse process a region of the cell membrane will dimple inwards and eventually pinch off, enclosing a portion of the extracellular fluid to transport it into the cell. Endocytosis and exocytosis rely on very different molecular machinery to function, but the two processes are intimately linked and could not work without each other. The primary mechanism this interdependence is the sheer volume of lipid material involved.<ref name=Gundelfinger2003>{{cite journal |author=Gundelfinger ED, Kessels MM, Qualmann B |title=Temporal and spatial coordination of exocytosis and endocytosis |journal=Nat. Rev. Mol. Cell Biol. |volume=4 |issue=2 |pages=127–39 |date=February 2003 |pmid=12563290 |doi=10.1038/nrm1016 }}</ref> In a typical cell, an area of bilayer equivalent to the entire plasma membrane will travel through the endocytosis/exocytosis cycle in about half an hour.<ref name=Steinman1976>{{cite journal |author=Steinman RM, Brodie SE, Cohn ZA |title=Membrane flow during pinocytosis. A stereologic analysis |journal=J. Cell Biol. |volume=68 |issue=3 |pages=665–87 |date=March 1976 |pmid=1030706 |pmc=2109655 |url=http://www.jcb.org/cgi/pmidlookup?view=long&pmid=1030706 |doi=10.1083/jcb.68.3.665}}</ref> If these two processes were not balancing each other the cell would either balloon outward to an unmanageable size or completely deplete its plasma membrane within a matter of minutes.
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| ===Electroporation===
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| {{further2|[[Electroporation]]}}
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| Electroporation is the rapid increase in bilayer permeability induced by the application of a large artificial electric field across the membrane. Experimentally, electroporation is used to introduce hydrophilic molecules into cells. It is a particularly useful technique for large highly charged molecules such as [[DNA]] which would never passively diffuse across the hydrophobic bilayer core.<ref name=Neumann1982>{{cite journal |author=Neumann E, Schaefer-Ridder M, Wang Y, Hofschneider PH |title=Gene transfer into mouse lyoma cells by electroporation in high electric fields |journal=EMBO J. |volume=1 |issue=7 |pages=841–5 |year=1982 |pmid=6329708 |pmc=553119 }}</ref> Because of this, electroporation is one of the key methods of [[transfection]] as well as bacterial [[Transformation (genetics)|transformation]]. It has even been proposed that electroporation resulting from [[lightning]] strikes could be a mechanism of natural [[horizontal gene transfer]].<ref name="Demanèche2001">{{cite journal |author=Demanèche S, Bertolla F, Buret F, ''et al.'' |title=Laboratory-scale evidence for lightning-mediated gene transfer in soil |journal=Appl. Environ. Microbiol. |volume=67 |issue=8 |pages=3440–4 |date=August 2001 |pmid=11472916 |pmc=93040 |doi=10.1128/AEM.67.8.3440-3444.2001 }}</ref>
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| This increase in permeability primarily affects transport of ions and other hydrated species, indicating that the mechanism is the creation of nm-scale water-filled holes in the membrane. Although electroporation and [[dielectric breakdown]] both result from application of an electric field, the mechanisms involved are fundamentally different. In dielectric breakdown the barrier material is ionized, creating a conductive pathway. The material alteration is thus chemical in nature. In contrast, during electroporation the lipid molecules are not chemically altered but simply shift position, opening up a pore which acts as the conductive pathway through the bilayer as it is filled with water.
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| ==Mechanics==
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| {{Further2|[[Lipid bilayer mechanics]]}}
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| [[Image:Pore schematic.svg|thumb|280px|Schematic showing two possible conformations of the lipids at the edge of a pore. In the top image the lipids have not rearranged, so the pore wall is hydrophobic. In the bottom image some of the lipid heads have bent over, so the pore wall is hydrophilic.]]
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| Lipid bilayers are large enough structures to have some of the mechanical properties of liquids or solids. The area compression modulus K<sub>a</sub>, bending modulus K<sub>b</sub>, and edge energy <math>\Lambda</math>, can be used to describe them. Solid lipid bilayers also have a [[shear modulus]], but like any liquid, the shear modulus is zero for fluid bilayers. These mechanical properties affect how the membrane functions. K<sub>a</sub> and K<sub>b</sub> affect the ability of proteins and small molecules to insert into the bilayer,<ref name=Garcia2004>{{cite journal |author=Garcia ML |title=Ion channels: gate expectations |journal=Nature |volume=430 |issue=6996 |pages=153–5 |date=July 2004 |pmid=15241399 |doi=10.1038/430153a |bibcode = 2004Natur.430..153G }}</ref><ref name=McIntosh2006>{{cite journal |author=McIntosh TJ, Simon SA |title=Roles of Bilayer Material Properties in Function and Distribution of Membrane Proteins |journal=Annu. Rev. Biophys. Biomol. Struct. |volume=35 |issue=1 |pages=177–98 |year=2006 |doi=10.1146/annurev.biophys.35.040405.102022 |pmid=16689633}}</ref> and bilayer mechanical properties have been shown to alter the function of mechanically activated ion channels.<ref name=Suchyna2004>{{cite journal |author=Suchyna TM, Tape SE, Koeppe RE, Andersen OS, Sachs F, Gottlieb PA |title=Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers |journal=Nature |volume=430 |issue=6996 |pages=235–40 |date=July 2004 |pmid=15241420 |doi=10.1038/nature02743 |bibcode = 2004Natur.430..235S }}</ref> Bilayer mechanical properties also govern what types of stress a cell can withstand without tearing. Although lipid bilayers can easily bend, most cannot stretch more than a few percent before rupturing.<ref name=Hallett1993>{{cite journal |author=Hallett FR, Marsh J, Nickel BG, Wood JM |title=Mechanical properties of vesicles. II. A model for osmotic swelling and lysis |journal=Biophys. J. |volume=64 |issue=2 |pages=435–42 |date=February 1993 |pmid=8457669 |pmc=1262346 |doi=10.1016/S0006-3495(93)81384-5 |bibcode=1993BpJ....64..435H}}</ref>
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| As discussed in the Structure and organization section, the hydrophobic attraction of lipid tails in water is the primary force holding lipid bilayers together. Thus, the elastic modulus of the bilayer is primarily determined by how much extra area is exposed to water when the lipid molecules are stretched apart.<ref name=Boal2002>{{cite book |author=Boal, David H. |title=Mechanics of the cell |publisher=Cambridge University Press |location=Cambridge, UK |year=2001 |pages= |isbn=0-521-79681-4 }}</ref> It is not surprising given this understanding of the forces involved that studies have shown that K<sub>a</sub> varies strongly with [[osmotic pressure]] <ref name=Rutkowski1991>{{cite journal |author=Rutkowski CA, Williams LM, Haines TH, Cummins HZ |title=The elasticity of synthetic phospholipid vesicles obtained by photon correlation spectroscopy |journal=Biochemistry |volume=30 |issue=23 |pages=5688–96 |date=June 1991 |pmid=2043611 |doi=10.1021/bi00237a008 }}</ref> but only weakly with tail length and unsaturation.<ref name="Rawicz2000"/> Because the forces involved are so small, it is difficult to experimentally determine K<sub>a</sub>. Most techniques require sophisticated microscopy and very sensitive measurement equipment.<ref name="Steltenkamp2006"/><ref name=Evans2003>{{cite journal |author=Evans E, Heinrich V, Ludwig F, Rawicz W |title=Dynamic tension spectroscopy and strength of biomembranes |journal=Biophys. J. |volume=85 |issue=4 |pages=2342–50 |date=October 2003 |pmid=14507698 |pmc=1303459 |doi=10.1016/S0006-3495(03)74658-X |bibcode=2003BpJ....85.2342E}}</ref>
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| In contrast to K<sub>a</sub>, which is a measure of how much energy is needed to stretch the bilayer, K<sub>b</sub> is a measure of how much energy is needed to bend or flex the bilayer. Formally, bending modulus is defined as the energy required to deform a membrane from its intrinsic curvature to some other curvature. Intrinsic curvature is defined by the ratio of the diameter of the head group to that of the tail group. For two-tailed PC lipids, this ratio is nearly one so the intrinsic curvature is nearly zero. If a particular lipid has too large a deviation from zero intrinsic curvature it will not form a bilayer and will instead form other phases such as [[micelle]]s or inverted micelles. Typically, K<sub>b</sub> is not measured experimentally but rather is calculated from measurements of K<sub>a</sub> and bilayer thickness, since the three parameters are related.
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| <math>\Lambda</math> is a measure of how much energy it takes to expose a bilayer edge to water by tearing the bilayer or creating a hole in it. The origin of this energy is the fact that creating such an interface exposes some of the lipid tails to water, but the exact orientation of these border lipids is unknown. There is some evidence that both hydrophobic (tails straight) and hydrophilic (heads curved around) pores can coexist.<ref name=Weaver1996>{{cite journal |author=Weaver JC, Chizmadzhev YA |title=Theory of electroporation: A review |journal=Biochemistry and Bioenergetics |volume=41 |issue= 2|pages=135–60 |year=1996 |doi=10.1016/S0302-4598(96)05062-3}}</ref>
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| ==Fusion==
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| {{see also|Lipid bilayer fusion|Interbilayer forces in membrane fusion}}
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| [[Image:Lipid bilayer fusion.svg|right|thumb|280px| Illustration of lipid vesicles fusing showing two possible outcomes: hemifusion and full fusion. In hemifusion only the outer bilayer leaflets mix. In full fusion both leaflets as well as the internal contents mix.]]
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| [[Lipid bilayer fusion|Fusion]] is the process by which two lipid bilayers merge, resulting in one connected structure. If this fusion proceeds completely through both leaflets of both bilayers, a water-filled bridge is formed and the solutions contained by the bilayers can mix. Alternatively, if only one leaflet from each bilayer is involved in the fusion process, the bilayers are said to be hemifused. Fusion is involved in many cellular processes, particularly in [[eukaryote]]s since the eukaryotic cell is extensively sub-divided by lipid bilayer membranes. [[Exocytosis]], [[fertilization]] of an [[egg (biology)|egg]] by [[sperm]] and transport of waste products to the [[lysozome]] are a few of the many eukaryotic processes that rely on some form of fusion. Even the entry of pathogens can be governed by fusion, as many bilayer-coated [[virus]]es have dedicated fusion proteins to gain entry into the host cell.
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| There are four fundamental steps in the fusion process.<ref name=Yeagle1993/> First, the involved membranes must aggregate, approaching each other to within several nanometers. Second, the two bilayers must come into very close contact (within a few angstroms). To achieve this close contact, the two surfaces must become at least partially dehydrated, as the bound surface water normally present causes bilayers to strongly repel. The presence of ions, particularly divalent cations like magnesium and calcium, strongly affects this step.<ref name=Papahadjopoulos1990>{{cite journal |author=Papahadjopoulos D, Nir S, Düzgünes N |title=Molecular mechanisms of calcium-induced membrane fusion |journal=J. Bioenerg. Biomembr. |volume=22 |issue=2 |pages=157–79 |date=April 1990 |pmid=2139437 |doi=10.1007/BF00762944 }}</ref><ref name=Leventis1986>{{cite journal |author=Leventis R, Gagné J, Fuller N, Rand RP, Silvius JR |title=Divalent cation induced fusion and lipid lateral segregation in phosphatidylcholine-phosphatidic acid vesicles |journal=Biochemistry |volume=25 |issue=22 |pages=6978–87 |date=November 1986 |pmid=3801406 |doi=10.1021/bi00370a600 }}</ref> One of the critical roles of calcium in the body is regulating membrane fusion. Third, a destabilization must form at one point between the two bilayers, locally distorting their structures. The exact nature of this distortion is not known. One theory is that a highly curved "stalk" must form between the two bilayers.<ref name=Markin1984>{{cite journal |author=Markin VS, Kozlov MM, Borovjagin VL |title=On the theory of membrane fusion. The stalk mechanism |journal=Gen. Physiol. Biophys. |volume=3 |issue=5 |pages=361–77 |date=October 1984 |pmid=6510702 }}</ref> Proponents of this theory believe that it explains why phosphatidylethanolamine, a highly curved lipid, promotes fusion.<ref name=Chernomordik2003>{{cite journal |author=Chernomordik LV, Kozlov MM |title=Protein-lipid interplay in fusion and fission of biological membranes |journal=Annu. Rev. Biochem. |volume=72 |issue= 1|pages=175–207 |year=2003 |pmid=14527322 |doi=10.1146/annurev.biochem.72.121801.161504 }}</ref> Finally, in the last step of fusion, this point defect grows and the components of the two bilayers mix and diffuse away from the site of contact.
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| [[Image:Membrane fusion via stalk formation.jpg|left|thumb|420px| Schematic illustration of the process of fusion through stalk formation.]]
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| [[Image:Exocytosis-machinery.jpg|right|thumb|330px| Diagram of the action of SNARE proteins docking a vesicle for exocytosis. Complementary versions of the protein on the vesicle and the target membrane bind and wrap around each other, drawing the two bilayers close together in the process.<ref name="Georgiev2007">{{cite book
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| | last = Georgiev
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| | first = Danko D .
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| | coauthors = James F . Glazebrook
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| | chapter = Subneuronal processing of information by solitary waves and stochastic processes
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| | title = Nano and Molecular Electronics Handbook
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| | publisher = CRC Press
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| | series = Nano and Microengineering Series
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| | editor-last = Lyshevski
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| | editor-first = Sergey Edward
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| | volume =
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| | pages = 17–1–17–41
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| | year = 2007
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| | url = http://www.crcnetbase.com/doi/abs/10.1201/9781420008142.ch17
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| | isbn = 978-0-8493-8528-5
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| }}</ref>]]
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| The situation is further complicated when considering fusion ''in vivo'' since biological fusion is almost always regulated by the action of [[Membrane protein|membrane-associated proteins]]. The first of these proteins to be studied were the viral fusion proteins, which allow an enveloped [[virus]] to insert its genetic material into the host cell (enveloped viruses are those surrounded by a lipid bilayer; some others have only a protein coat).[[Eukaryotic]] cells also use fusion proteins, the best studied of which are the [[SNARE (protein)|SNAREs]]. SNARE proteins are used to direct all [[Vesicle (biology)|vesicular]] intracellular trafficking. Despite years of study, much is still unknown about the function of this protein class. In fact, there is still an active debate regarding whether SNAREs are linked to early docking or participate later in the fusion process by facilitating hemifusion.<ref name=Chen2001>{{cite journal |author=Chen YA, Scheller RH |title=SNARE-mediated membrane fusion |journal=Nat. Rev. Mol. Cell Biol. |volume=2 |issue=2 |pages=98–106 |date=February 2001 |pmid=11252968 |doi=10.1038/35052017 }}</ref>
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| In studies of molecular and cellular biology it is often desirable to artificially induce fusion. The addition of [[polyethylene glycol]] (PEG) causes fusion without significant aggregation or biochemical disruption. This procedure is now used extensively, for example by fusing [[B-cell]]s with [[melanoma]] cells.<ref name=Kohler1975>{{cite journal |author=Köhler G, Milstein C |title=Continuous cultures of fused cells secreting antibody of predefined specificity |journal=Nature |volume=256 |issue=5517 |pages=495–7 |date=August 1975 |pmid=1172191 |doi=10.1038/256495a0 |bibcode=1975Natur.256..495K}}</ref> The resulting “[[hybridoma]]” from this combination expresses a desired [[antibody]] as determined by the B-cell involved, but is immortalized due to the melanoma component. Fusion can also be artificially induced through [[electroporation]] in a process known as electrofusion. It is believed that this phenomenon results from the [[Lipid bilayer mechanics|energetically active edges]] formed during electroporation, which can act as the local defect point to nucleate stalk growth between two bilayers.<ref name=Jordan1989>{{cite book |author=Jordan, Carol A.; Neumann, Eberhard; Sowershi mason, Arthur E. |title=Electroporation and electrofusion in cell biology |publisher=Plenum Press |location=New York |year=1989 |isbn=0-306-43043-6 }}</ref>
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| ==Model systems==
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| {{further2|[[Model lipid bilayers]]}}
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| Lipid bilayers can be created artificially in the lab to allow researchers to perform experiments that cannot be done with natural bilayers. These synthetic systems are called model lipid bilayers. There are many different types of model bilayers, each having experimental advantages and disadvantages. They can be made with either synthetic or natural lipids. Among the most common model systems are:
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| * [[Model lipid bilayers#Black lipid membranes (BLM)|Black lipid membranes (BLM)]]
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| * [[Model lipid bilayers#Supported lipid bilayers (SLB)|Supported lipid bilayers (SLB)]]
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| * [[Model lipid bilayers#Tethered Bilayer Lipid Membranes (t-BLM)|Tethered Bilayer Lipid Membranes (t-BLM)]]
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| * [[Model lipid bilayers#Vesicles|Vesicles]]
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| ==Commercial applications==
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| To date, the most successful commercial application of lipid bilayers has been the use of [[liposome]]s for drug delivery, especially for cancer treatment. (Note- the term “liposome” is essentially synonymous with “[[Vesicle (biology)|vesicle]]” except that vesicle is a general term for the structure whereas liposome only refers to artificial, not natural vesicles) The basic idea of liposomal drug delivery is that the drug is encapsulated in solution inside the liposome then injected into the patient. These drug-loaded liposomes travel through the system until they bind at the target site and rupture, releasing the drug. In theory, liposomes should make an ideal drug delivery system since they can isolate nearly any hydrophilic drug, can be grafted with molecules to target specific tissues and can be relatively non-toxic since the body possesses biochemical pathways for [[Metabolize|degrading]] lipids.<ref name=Immordino2006>{{cite journal |author=Immordino ML, Dosio F, Cattel L |title=Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential |journal=Int J Nanomedicine |volume=1 |issue=3 |pages=297–315 |year=2006 |pmid=17717971 |pmc=2426795 |doi=10.2217/17435889.1.3.297 }}</ref>
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| The first generation of drug delivery liposomes had a simple lipid composition and suffered from several limitations. Circulation in the bloodstream was extremely limited due to both [[renal]] clearing and [[phagocytosis]]. Refinement of the lipid composition to tune fluidity, surface charge density and surface hydration resulted in vesicles that adsorb fewer proteins from [[blood serum|serum]] and thus are less readily recognized by the [[immune system]].<ref name=Chonn1992>{{cite journal |author=Chonn A, Semple SC, Cullis PR |title=Association of blood proteins with large unilamellar liposomes in vivo. Relation to circulation lifetimes |journal=J. Biol. Chem. |volume=267 |issue=26 |pages=18759–65 |date=15 September 1992|pmid=1527006 |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=1527006 }}</ref> The most significant advance in this area was the grafting of [[polyethylene glycol]] (PEG) onto the liposome surface to produce “stealth” vesicles which circulate over long times without immune or renal clearing.<ref name=Boris1997>{{cite journal |author=Boris EH, Winterhalter M, Frederik PM, Vallner JJ, Lasic DD |title=Stealth liposomes: from theory to product |journal=Advanced Drug Delivery Reviews |volume=24 |issue= 2–3|pages=165–77 |year=1997 |doi=10.1016/S0169-409X(96)00456-5}}</ref>
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| The first stealth liposomes were passively targeted at [[tumor]] tissues. Because tumors induce rapid and uncontrolled [[angiogenesis]] they are especially “leaky” and allow liposomes to exit the bloodstream at a much higher rate than normal tissue would.<ref name=Maeda2001>{{cite journal |author=Maeda H, Sawa T, Konno T |title=Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS |journal=J Control Release |volume=74 |issue=1–3 |pages=47–61 |date=July 2001 |pmid=11489482 |url=http://linkinghub.elsevier.com/retrieve/pii/S0168365901003091 |doi=10.1016/S0168-3659(01)00309-1}}</ref> More recently{{when|date=January 2011}} work has been undertaken to graft [[antibodies]] or other molecular markers onto the liposome surface in the hope of actively binding them to a specific cell or tissue type.<ref name=Lopes1999>{{cite journal |author=Lopes DE, Menezes DE, Kirchmeier MJ, Gagne JF |title=Cellular trafficking and cytotoxicity of anti-CD19-targeted liposomal doxorubicin in B lymphoma cells |journal=Journal of Liposome Research |volume=9 |issue= 2|pages=199–228 |year=1999 |doi=10.3109/08982109909024786}}</ref> Some examples of this approach are already in clinical trials.<ref name=Matsumura2004>{{cite journal |author=Matsumura Y, Gotoh M, Muro K, ''et al.'' |title=Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer |journal=Ann. Oncol. |volume=15 |issue=3 |pages=517–25 |date=March 2004 |pmid=14998859 |url=http://annonc.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=14998859 |doi=10.1093/annonc/mdh092}}</ref>
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| Another potential application of lipid bilayers is the field of [[biosensor]]s. Since the lipid bilayer is the barrier between the interior and exterior of the cell it is also the site of extensive signal transduction. Researchers over the years have tried to harness this potential to develop a bilayer-based device for clinical diagnosis or bioterrorism detection. Progress has been slow in this area and, although a few companies have developed automated lipid-based detection systems, they are still targeted at the research community. These include Biacore Life Sciences, which offers a disposable chip for utilizing lipid bilayers in studies of binding kinetics<ref name=Biacore>[http://www.biacore.com/lifesciences/products/systems_overview/A100/system_information/index.html Biacore A100 System Information]. Biacore Inc. Retrieved Feb 12, 2009.</ref> and Nanion Inc which has developed an [[Planar patch clamp|automated patch clamping]] system.<ref>[http://www.nanion.de/pdf/PlanarPatchClamping.pdf Nanion Technologies. Automated Patch Clamp]. Retrieved Feb 28, 2010. (PDF)</ref> Other, more exotic applications are also being pursued such as the use of lipid bilayer membrane pores for [[DNA sequencing]] by Oxford Nanolabs. To date, this technology has not proven commercially viable.
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| A supported lipid bilayer (SLB) as described above has achieved commercial success as a screening technique to measure the permeability of drugs. This '''p'''arallel '''a'''rtificial '''m'''embrane '''p'''ermeability '''a'''ssay [[PAMPA]] technique measures the permeability across specifically formulated lipid cocktail(s) found to be highly correlated with [[Caco-2]] cultures,<ref>Bermejo, M. et al. (2004). PAMPA – a drug absorption in vitro model 7. Comparing rat in situ, [[Caco-2]], and PAMPA permeability of fluoroquinolones. Pharm. Sci., '''21:''' 429-441.</ref><ref>Avdeef, A. et al. (2005). Caco-2 permeability of weakly basic drugs predicted with the Double-Sink PAMPA pKaflux method. Pharm. Sci., '''24:''' 333-349.</ref> the [[gastrointestinal tract]],<ref>Avdeef, A. et al. (2004). PAMPA – a drug absorption in vitro model 11. Matching the in vivo unstirred water layer thickness by individual-well stirring in microtitre plates. Pharm. Sci., '''22:''' 365-374.</ref> [[blood–brain barrier]]<ref>Dagenais, C. et al. (2009). P-glycoprotein deficient mouse in situ blood–brain barrier permeability and its prediction using an in combo PAMPA model. Eur. J. Phar. Sci., '''38(2):''' 121-137.</ref> and skin.<ref>Sinkó, B. et al. (2009). A PAMPA Study of the Permeability-Enhancing Effect of New Ceramide Analogues. Chemistry & Biodiversity, '''6:''' 1867-1874.</ref>
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| ==History==
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| {{Further2|[[History of cell membrane theory]]}}
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| By the early twentieth century scientists had come to believe that cells are surrounded by a thin oil-like barrier,<ref name=Loeb1904>{{cite journal |author=Loeb J |title=The recent development of Biology |journal=Science |volume=20 |issue=519 |pages=777–786 |date=December 1904 |pmid=17730464 |doi=10.1126/science.20.519.777 |bibcode = 1904Sci....20..777L }}</ref> but the structural nature of this membrane was not known. Two experiments in 1925 laid the groundwork to fill in this gap. By measuring the [[capacitance]] of [[erythrocyte]] solutions, Hugo Fricke determined that the cell membrane was 3.3 nm thick.<ref name=Fricke1925>{{cite journal |author=Fricke H |title=The electrical capacity of suspensions with special reference to blood |journal=Journal of General Physiology |volume=9 |issue= 2|pages=137–52 |year=1925 |pmid=19872238 |pmc=2140799 |doi=10.1085/jgp.9.2.137}}</ref>
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| Although the results of this experiment were accurate, Fricke misinterpreted the data to mean that the cell membrane is a single molecular layer. Prof. Dr. Evert Gorter<ref name=Gorterbio>{{cite journal |author=Dooren L J, Wiedemann L R |title=On bimolecular layers of lipids on the chromocytes of the blood |journal=Journal of European Journal of Pediatrics |volume=145 |issue=5 |pages=329 |year=1986 |doi=10.1007/BF00439232}}</ref> (1881–1954) and F. Grendel of Leiden University approached the problem from a different perspective, spreading the erythrocyte lipids as a monolayer on a [[Langmuir-Blodgett trough]]. When they compared the area of the monolayer to the surface area of the cells, they found a ratio of two to one.<ref name=Gorter1925>{{cite journal |author=Gorter E, Grendel F |title=On bimolecular layers of lipids on the chromocytes of the blood |journal=Journal of Experimental Medicine |volume=41 |issue= 4|pages=439–43 |year=1925 |pmid=19868999 |pmc=2130960 |doi=10.1084/jem.41.4.439}}</ref> Later analyses showed several errors and incorrect assumptions with this experiment but, serendipitously, these errors canceled out and from this flawed data Gorter and Grendel drew the correct conclusion- that the cell membrane is a lipid bilayer.<ref name=Yeagle1993>{{cite book |author=Yeagle, Philip |title=The membranes of cells |publisher=Academic Press |location=Boston |year=1993 |edition=2nd |isbn=0-12-769041-7 }}</ref>
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| This theory was confirmed through the use of [[electron microscopy]] in the late 1950s. Although he did not publish the first electron microscopy study of lipid bilayers<ref name="Sjöstrand1958">{{cite journal |author=Sjöstrand FS, Andersson-Cedergren E, Dewey MM |title=The ultrastructure of the intercalated discs of frog, mouse and guinea pig cardiac muscle |journal=J. Ultrastruct. Res. |volume=1 |issue=3 |pages=271–87 |date=April 1958 |pmid=13550367 |doi=10.1016/S0022-5320(58)80008-8 }}</ref> J. David Robertson was the first to assert that the two dark electron-dense bands were the headgroups and associated proteins of two apposed lipid monolayers.<ref name=Robertson1960>{{cite journal |author=Robertson JD |title=The molecular structure and contact relationships of cell membranes |journal=Prog. Biophys. Mol. Biol. |volume=10 |issue= |pages=343–418 |year=1960 |pmid=13742209 }}</ref><ref name=Robertson1959>{{cite journal |author=Robertson JD |title=The ultrastructure of cell membranes and their derivatives |journal=Biochem. Soc. Symp. |volume=16 |issue= |pages=3–43 |year=1959 |pmid=13651159 }}</ref> In this body of work, Robertson put forward the concept of the “unit membrane.” This was the first time the bilayer structure had been universally assigned to all cell membranes as well as [[organelle]] membranes.
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| Around the same time the development of model membranes confirmed that the lipid bilayer is a stable structure that can exist independently of proteins. By “painting” a solution of lipid in organic solvent across an aperture, Mueller and Rudin were able to create an artificial bilayer and determine that this exhibited lateral fluidity, high electrical resistance and self-healing in response to puncture,<ref name=Mueller1962>{{cite journal |author=Mueller P, Rudin DO, Tien HT, Wescott WC |title=Reconstitution of cell membrane structure in vitro and its transformation into an excitable system |journal=Nature |volume=194 |issue= 4832|pages=979–80 |date=June 1962 |pmid=14476933 |doi=10.1038/194979a0 |bibcode = 1962Natur.194..979M }}</ref> all of which are properties of a natural cell membrane. A few years later, [[Alec Douglas Bangham|Alec Bangham]] showed that bilayers, in the form of lipid vesicles, could also be formed simply by exposing a dried lipid sample to water.<ref name=Bangham1964>{{cite pmid|14187392}}</ref> This was an important advance since it demonstrated that lipid bilayers form spontaneously via [[self assembly]] and do not require a patterned support structure.
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| ==See also==
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| <div style="-moz-column-count:2; column-count:2;">
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| * [[:Category: surfactants]]
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| * [[Membrane protein]]
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| </div> | |
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| ==References==
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| {{Reflist|2}}
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| ==External links==
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| * [http://avantilipids.com/ Avanti Lipids] One of the largest commercial suppliers of lipids. Technical information on lipid properties and handling and lipid bilayer preparation techniques.
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| * [http://www.lipidat.ul.ie/search.htm LIPIDAT] An extensive database of lipid physical properties
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| * [http://blanco.biomol.uci.edu/Bilayer_Struc.html Structure of Fluid Lipid Bilayers] Simulations and publication links related to the cross sectional structure of lipid bilayers.
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| * [http://biomodel.uah.es/en/model2/bilayer/en/inicio.htm Lipid Bilayers and the Gramicidin Channel] (requires Java plugin) Pictures and movies showing the results of molecular dynamics simulations of lipid bilayers.
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| * [http://blanco.biomol.uci.edu/Bilayer_Struc.html Structure of Fluid Lipid Bilayers], from the Stephen White laboratory at [[University of California, Irvine]]
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| * [http://telstar.ote.cmu.edu/biology/MembranePage/index2.html Animations of lipid bilayer dynamics] (requires Flash plugin)
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| {{Membrane lipids}}
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| {{good article}}
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| {{DEFAULTSORT:Lipid Bilayer}}
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| [[Category:Biological matter]]
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| [[Category:Membrane biology]]
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