Cross-link

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Vulcanization is an example of cross-linking. Schematic presentation of two "polymer chains" (blue and green) cross-linked after the vulcanization of natural rubber with sulfur (n = 0, 1, 2, 3, ...). Vulcanization of POLYIsoprene V.2.png
Vulcanization is an example of cross-linking. Schematic presentation of two "polymer chains" (blue and green) cross-linked after the vulcanization of natural rubber with sulfur (n = 0, 1, 2, 3, ...).
IUPAC definition

A small region in a macromolecule from which at least four chains
emanate, and formed by reactions involving sites or groups on existing
macromolecules or by interactions between existing macromolecules.

Contents

Notes

1. The small region may be an atom, a group of atoms, or a number of
branch points connected by bonds, groups of atoms, or oligomeric chains.

2. In the majority of cases, a crosslink is a covalent structure but the term
is also used to describe sites of weaker chemical interactions, portions of
crystallites, and even physical interactions and entanglements. [1]

In chemistry and biology a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural polymers (such as proteins).

In polymer chemistry "cross-linking" usually refers to the use of cross-links to promote a change in the polymers' physical properties.

When "crosslinking" is used in the biological field, it refers to the use of a probe to link proteins together to check for protein–protein interactions, as well as other creative cross-linking methodologies.[ not verified in body ]

Although the term is used to refer to the "linking of polymer chains" for both sciences, the extent of crosslinking and specificities of the crosslinking agents vary greatly.

Synthetic polymers

Chemical reactions associated with crosslinking of drying oils, the process that produces linoleum. DryOilSteps.svg
Chemical reactions associated with crosslinking of drying oils, the process that produces linoleum.

Crosslinking generally involves covalent bonds that join two polymer chains. The term curing refers to the crosslinking of thermosetting resins, such as unsaturated polyester and epoxy resin, and the term vulcanization is characteristically used for rubbers. [2] When polymer chains are crosslinked, the material becomes more rigid. The mechanical properties of a polymer depend strongly on the cross-link density. Low cross-link densities increase the viscosities of polymer melts. Intermediate cross-link densities transform gummy polymers into materials that have elastomeric properties and potentially high strengths. Very high cross-link densities can cause materials to become very rigid or glassy, such as phenol-formaldehyde materials. [3]

Typical vinyl ester resin derived from bisphenol A diglycidyl ether. Free-radical polymerization gives a highly crosslinked polymer. MethmethacrylateBPA-glyc.png
Typical vinyl ester resin derived from bisphenol A diglycidyl ether. Free-radical polymerization gives a highly crosslinked polymer.

In one implementation, unpolymerized or partially polymerized resin is treated with a crosslinking reagent. In vulcanization, sulfur is the cross-linking agent. Its introduction changes rubber to a more rigid, durable material associated with car and bike tires. This process is often called sulfur curing. In most cases, cross-linking is irreversible, and the resulting thermosetting material will degrade or burn if heated, without melting. Chemical covalent cross-links are stable mechanically and thermally. Therefore, cross-linked products like car tires cannot be recycled easily. A class of polymers known as thermoplastic elastomers rely on physical cross-links in their microstructure to achieve stability, and are widely used in non-tire applications, such as snowmobile tracks, and catheters for medical use. They offer a much wider range of properties than conventional cross-linked elastomers because the domains that act as cross-links are reversible, so can be reformed by heat. The stabilizing domains may be non-crystalline (as in styrene-butadiene block copolymers) or crystalline as in thermoplastic copolyesters.

The compound bis(triethoxysilylpropyl)tetrasulfide is a cross-linking agent: the siloxy groups link to silica and the polysulfide groups vulcanize with polyolefins. Si69.svg
The compound bis(triethoxysilylpropyl)tetrasulfide is a cross-linking agent: the siloxy groups link to silica and the polysulfide groups vulcanize with polyolefins.

Alkyd enamels, the dominant type of commercial oil-based paint, cure by oxidative crosslinking after exposure to air. [5]

In contrast to chemical cross-links, physical cross-links are formed by weaker interactions. For example, sodium alginate gels upon exposure to calcium ions, which form ionic bonds that bridge between alginate chains. [6] Polyvinyl alcohol gels upon the addition of borax through hydrogen bonding between boric acid and the polymer's alcohol groups. [7] [8] Other examples of materials which form physically cross-linked gels include gelatin, collagen, agarose, and agar agar.

Measuring degree of crosslinking

Crosslinking is often measured by swelling tests. The crosslinked sample is placed into a good solvent at a specific temperature, and either the change in mass or the change in volume is measured. The more crosslinking, the less swelling is attainable. Based on the degree of swelling, the Flory Interaction Parameter (which relates the solvent interaction with the sample), and the density of the solvent, the theoretical degree of crosslinking can be calculated according to Flory's Network Theory. [9] Two ASTM standards are commonly used to describe the degree of crosslinking in thermoplastics. In ASTM D2765, the sample is weighed, then placed in a solvent for 24 hours, weighed again while swollen, then dried and weighed a final time. [10] The degree of swelling and the soluble portion can be calculated. In another ASTM standard, F2214, the sample is placed in an instrument that measures the height change in the sample, allowing the user to measure the volume change. [11] The crosslink density can then be calculated.

In biology

Idealized structure of lignin, a highly crosslinked polymer that is the main structural material in many plants. Lignin structure.svg
Idealized structure of lignin, a highly crosslinked polymer that is the main structural material in many plants.

Lignin

Lignin is a highly crosslinked polymer that comprises the main structural material of higher plants. A hydrophobic material, it is derived from precursor monolignols. Heterogeneity arises from the diversity and degree of crosslinking between these lignols.

In DNA

HN1 (bis(2-chloroethyl)ethylamine), a DNA crosslinker. Like most crosslinkers, this molecule has two reactive groups. Ethyl-S.svg
HN1 (bis(2-chloroethyl)ethylamine), a DNA crosslinker. Like most crosslinkers, this molecule has two reactive groups.

Intrastrand DNA crosslinks have strong effects on organisms because these lesions interfere with transcription and replication. These effects can be put to good use (addressing cancer) or they can be lethal to the host organism. The drug cisplatin functions by formation of intrastrand crosslinks in DNA. [12] Other crosslinking agents include mustard gas, mitomycin, and psoralen. [13]

Proteins

In proteins, crosslinks are important in generating mechanically stable structures such as hair and wool, skin, and cartilage. Disulfide bonds are common crosslinks. [14] Isopeptide bond formation is another type of protein crosslink.

The process of applying a permanent wave to hair involves the breaking and reformation disulfide bonds. Typically a mercaptan such as ammonium thioglycolate is used for the breaking. Following this, the hair is curled and then "neutralized". The neutralizer is typically an acidic solution of hydrogen peroxide, which causes new disulfide bonds to form, thus permanently fixing the hair into its new configuration.

Compromised collagen in the cornea, a condition known as keratoconus, can be treated with clinical crosslinking. [15] In biological context crosslinking could play a role in atherosclerosis through advanced glycation end-products (AGEs), which have been implicated to induce crosslinking of collagen, which may lead to vascular stiffening. [16]

Research

Proteins can also be cross-linked artificially using small-molecule crosslinkers. This approach has been used to elucidate protein–protein interactions. [17] [18] [19] Crosslinkers bind only surface residues in relatively close proximity in the native state. Common crosslinkers include the imidoester crosslinker dimethyl suberimidate, the N-Hydroxysuccinimide-ester crosslinker BS3 and formaldehyde. Each of these crosslinkers induces nucleophilic attack of the amino group of lysine and subsequent covalent bonding via the crosslinker. The zero-length carbodiimide crosslinker EDC functions by converting carboxyls into amine-reactive isourea intermediates that bind to lysine residues or other available primary amines. SMCC or its water-soluble analog, Sulfo-SMCC, is commonly used to prepare antibody-hapten conjugates for antibody development. An in-vitro cross-linking method is PICUP (photo-induced cross-linking of unmodified proteins). [20] Typical reagents are ammonium persulfate (APS), an electron acceptor, the photosensitizer [[tris(bipyridine)ruthenium(II) chloride|tris-bipyridylruthenium (II) cation ([Ru(bpy)3]2+). [20] In in-vivo crosslinking of protein complexes, cells are grown with photoreactive diazirine analogs to leucine and methionine, which are incorporated into proteins. Upon exposure to ultraviolet light, the diazirines are activated and bind to interacting proteins that are within a few ångströms of the photo-reactive amino acid analog (UV cross-linking). [21]

See also

Related Research Articles

<span class="mw-page-title-main">Biopolymer</span> Polymer produced by a living organism

Biopolymers are natural polymers produced by the cells of living organisms. Like other polymers, biopolymers consist of monomeric units that are covalently bonded in chains to form larger molecules. There are three main classes of biopolymers, classified according to the monomers used and the structure of the biopolymer formed: polynucleotides, polypeptides, and polysaccharides. The Polynucleotides, RNA and DNA, are long polymers of nucleotides. Polypeptides include proteins and shorter polymers of amino acids; some major examples include collagen, actin, and fibrin. Polysaccharides are linear or branched chains of sugar carbohydrates; examples include starch, cellulose, and alginate. Other examples of biopolymers include natural rubbers, suberin and lignin, cutin and cutan, melanin, and polyhydroxyalkanoates (PHAs).

<span class="mw-page-title-main">Polymer</span> Substance composed of macromolecules with repeating structural units

A polymer (;) is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic and natural polymers play essential and ubiquitous roles in everyday life. Polymers range from familiar synthetic plastics such as polystyrene to natural biopolymers such as DNA and proteins that are fundamental to biological structure and function. Polymers, both natural and synthetic, are created via polymerization of many small molecules, known as monomers. Their consequently large molecular mass, relative to small molecule compounds, produces unique physical properties including toughness, high elasticity, viscoelasticity, and a tendency to form amorphous and semicrystalline structures rather than crystals.

<span class="mw-page-title-main">Thermosetting polymer</span> Polymer obtained by irreversibly hardening (curing) a resin

In materials science, a thermosetting polymer, often called a thermoset, is a polymer that is obtained by irreversibly hardening ("curing") a soft solid or viscous liquid prepolymer (resin). Curing is induced by heat or suitable radiation and may be promoted by high pressure or mixing with a catalyst. Heat is not necessarily applied externally, and is often generated by the reaction of the resin with a curing agent. Curing results in chemical reactions that create extensive cross-linking between polymer chains to produce an infusible and insoluble polymer network.

<span class="mw-page-title-main">Hydrogel</span> Soft water-rich polymer gel

A hydrogel is a biphasic material, a mixture of porous, permeable solids and at least 10% by weight or volume of interstitial fluid composed completely or mainly by water. In hydrogels the porous permeable solid is a water insoluble three dimensional network of natural or synthetic polymers and a fluid, having absorbed a large amount of water or biological fluids. These properties underpin several applications, especially in the biomedical area. Many hydrogels are synthetic, but some are derived from nature. The term 'hydrogel' was coined in 1894.

<span class="mw-page-title-main">Polyelectrolyte</span> Polymers whose repeating units bear an electrolyte group

Polyelectrolytes are polymers whose repeating units bear an electrolyte group. Polycations and polyanions are polyelectrolytes. These groups dissociate in aqueous solutions (water), making the polymers charged. Polyelectrolyte properties are thus similar to both electrolytes (salts) and polymers and are sometimes called polysalts. Like salts, their solutions are electrically conductive. Like polymers, their solutions are often viscous. Charged molecular chains, commonly present in soft matter systems, play a fundamental role in determining structure, stability and the interactions of various molecular assemblies. Theoretical approaches to describing their statistical properties differ profoundly from those of their electrically neutral counterparts, while technological and industrial fields exploit their unique properties. Many biological molecules are polyelectrolytes. For instance, polypeptides, glycosaminoglycans, and DNA are polyelectrolytes. Both natural and synthetic polyelectrolytes are used in a variety of industries.

<span class="mw-page-title-main">Molecular imprinting</span> Technique in polymer chemistry

Molecular imprinting is a technique to create template-shaped cavities in polymer matrices with predetermined selectivity and high affinity. This technique is based on the system used by enzymes for substrate recognition, which is called the "lock and key" model. The active binding site of an enzyme has a shape specific to a substrate. Substrates with a complementary shape to the binding site selectively bind to the enzyme; alternative shapes that do not fit the binding site are not recognized.

<span class="mw-page-title-main">Fibril</span> Thin Fibre

Fibrils are structural biological materials found in nearly all living organisms. Not to be confused with fibers or filaments, fibrils tend to have diameters ranging from 10–100 nanometers. Fibrils are not usually found alone but rather are parts of greater hierarchical structures commonly found in biological systems. Due to the prevalence of fibrils in biological systems, their study is of great importance in the fields of microbiology, biomechanics, and materials science.

Liquid crystal polymers (LCPs) are polymers with the property of liquid crystal, usually containing aromatic rings as mesogens. Despite uncrosslinked LCPs, polymeric materials like liquid crystal elastomers (LCEs) and liquid crystal networks (LCNs) can exhibit liquid crystallinity as well. They are both crosslinked LCPs but have different cross link density. They are widely used in the digital display market. In addition, LCPs have unique properties like thermal actuation, anisotropic swelling, and soft elasticity. Therefore, they can be good actuators and sensors. One of the most famous and classical applications for LCPs is Kevlar, a strong but light fiber with wide applications, notably bulletproof vests.  

Curing is a chemical process employed in polymer chemistry and process engineering that produces the toughening or hardening of a polymer material by cross-linking of polymer chains. Even if it is strongly associated with the production of thermosetting polymers, the term "curing" can be used for all the processes where a solid product is obtained from a liquid solution, such as with PVC plastisols.

<span class="mw-page-title-main">Immobilized enzyme</span>

An immobilized enzyme is an enzyme, with restricted mobility, attached to an inert, insoluble material—such as calcium alginate. This can provide increased resistance to changes in conditions such as pH or temperature. It also lets enzymes be held in place throughout the reaction, following which they are easily separated from the products and may be used again - a far more efficient process and so is widely used in industry for enzyme catalysed reactions. An alternative to enzyme immobilization is whole cell immobilization. Immobilized enzymes are easily to be handled, simply separated from their products, and can be reused.

Bissulfosuccinimidyl suberate (BS3) is a crosslinker used in biological research. It is a water-soluble version of disuccinimidyl suberate.

Photo-reactive amino acid analogs are artificial analogs of natural amino acids that can be used for crosslinking of protein complexes. Photo-reactive amino acid analogs may be incorporated into proteins and peptides in vivo or in vitro. Photo-reactive amino acid analogs in common use are photoreactive diazirine analogs to leucine and methionine, and para-benzoylphenylalanine. Upon exposure to ultraviolet light, they are activated and covalently bind to interacting proteins that are within a few angstroms of the photo-reactive amino acid analog.

<span class="mw-page-title-main">Interpenetrating polymer network</span>

An Interpenetrating polymer network (IPN) is a polymer comprising two or more networks which are at least partially interlaced on a polymer scale but not covalently bonded to each other. The network cannot be separated unless chemical bonds are broken. The two or more networks can be envisioned to be entangled in such a way that they are concatenated and cannot be pulled apart, but not bonded to each other by any chemical bond.

In polymer chemistry, in situ polymerization is a preparation method that occurs "in the polymerization mixture" and is used to develop polymer nanocomposites from nanoparticles. There are numerous unstable oligomers (molecules) which must be synthesized in situ for use in various processes. The in situ polymerization process consists of an initiation step followed by a series of polymerization steps, which results in the formation of a hybrid between polymer molecules and nanoparticles. Nanoparticles are initially spread out in a liquid monomer or a precursor of relatively low molecular weight. Upon the formation of a homogeneous mixture, initiation of the polymerization reaction is carried out by addition of an adequate initiator, which is exposed to a source of heat, radiation, etc. After the polymerization mechanism is completed, a nanocomposite is produced, which consists of polymer molecules bound to nanoparticles.

<span class="mw-page-title-main">Self-healing hydrogels</span> Type of hydrogel

Self-healing hydrogels are a specialized type of polymer hydrogel. A hydrogel is a macromolecular polymer gel constructed of a network of crosslinked polymer chains. Hydrogels are synthesized from hydrophilic monomers by either chain or step growth, along with a functional crosslinker to promote network formation. A net-like structure along with void imperfections enhance the hydrogel's ability to absorb large amounts of water via hydrogen bonding. As a result, hydrogels, self-healing alike, develop characteristic firm yet elastic mechanical properties. Self-healing refers to the spontaneous formation of new bonds when old bonds are broken within a material. The structure of the hydrogel along with electrostatic attraction forces drive new bond formation through reconstructive covalent dangling side chain or non-covalent hydrogen bonding. These flesh-like properties have motivated the research and development of self-healing hydrogels in fields such as reconstructive tissue engineering as scaffolding, as well as use in passive and preventive applications.

Hydrogels are three-dimensional networks consisting of chemically or physically cross-linked hydrophilic polymers. The insoluble hydrophilic structures absorb polar wound exudates and allow oxygen diffusion at the wound bed to accelerate healing. Hydrogel dressings can be designed to prevent bacterial infection, retain moisture, promote optimum adhesion to tissues, and satisfy the basic requirements of biocompatibility. Hydrogel dressings can also be designed to respond to changes in the microenvironment at the wound bed. Hydrogel dressings should promote an appropriate microenvironment for angiogenesis, recruitment of fibroblasts, and cellular proliferation.

Bio-inks are materials used to produce engineered/artificial live tissue using 3D printing. These inks are mostly composed of the cells that are being used, but are often used in tandem with additional materials that envelope the cells. The combination of cells and usually biopolymer gels are defined as a bio-ink. They must meet certain characteristics, including such as rheological, mechanical, biofunctional and biocompatibility properties, among others. Using bio-inks provides a high reproducibility and precise control over the fabricated constructs in an automated manner. These inks are considered as one of the most advanced tools for tissue engineering and regenerative medicine (TERM).

Topological polymers may refer to a polymeric molecule that possesses unique spatial features, such as linear, branched, or cyclic architectures. It could also refer to polymer networks that exhibit distinct topologies owing to special crosslinkers. When self-assembling or crosslinking in a certain way, polymeric species with simple topological identity could also demonstrate complicated topological structures in a larger spatial scale. Topological structures, along with the chemical composition, determine the macroscopic physical properties of polymeric materials.

<span class="mw-page-title-main">Hydrogel fiber</span>

Hydrogel fiber is a hydrogel made into a fibrous state, where its width is significantly smaller than its length. The hydrogel's specific surface area at fibrous form is larger than that of the bulk hydrogel, and its mechanical properties also changed accordingly. As a result of these changes, hydrogel fiber has a faster matter exchange rate and can be woven into different structures.

Covalent adaptable networks (CANs) are a type of polymer material that closely resemble thermosetting polymers (thermosets). However, they are distinguished from thermosets by the incorporation of dynamic covalent chemistry into the polymer network. When a stimulus (for example heat, light, pH, ...) is applied to the material, these dynamic bonds become active and can be broken or exchanged with other pending functional groups, allowing the polymer network to change its topology. This introduces reshaping, (re)processing and recycling into thermoset-like materials.

References

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  2. ↑ Hans Zweifel; Ralph D. Maier; Michael Schiller (2009). Plastics additives handbook (6th ed.). Munich: Hanser. p. 746. ISBN   978-3-446-40801-2.
  3. ↑ Gent, Alan N. (1 April 2018). Engineering with Rubber: How to Design Rubber Components. Hanser. ISBN   9781569902998 . Retrieved 1 April 2018– via Google Books.
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  5. ↑ Abraham, T.W.; Höfer, R. (2012), "Lipid-Based Polymer Building Blocks and Polymers", Polymer Science: A Comprehensive Reference, Elsevier, pp. 15–58, doi:10.1016/b978-0-444-53349-4.00253-3, ISBN   978-0-08-087862-1 , retrieved 2022-06-27
  6. ↑ Hecht, Hadas; Srebnik, Simcha (2016). "Structural Characterization of Sodium Alginate and Calcium Alginate". Biomacromolecules. 17 (6): 2160–2167. doi:10.1021/acs.biomac.6b00378. PMID   27177209.
  7. ↑ "Experiments: PVA polymer slime". Education: Inspiring your teaching and learning. Royal Society of Chemistry. 2016. Retrieved 2 April 2022. A solution of polyvinyl alcohol (PVA) can be made into a slime by adding borax solution, which creates cross-links between polymer chains.
  8. ↑ Casassa, E.Z; Sarquis, A.M; Van Dyke, C.H (1986). "The gelation of polyvinyl alcohol with borax: A novel class participation experiment involving the preparation and properties of a "slime"". Journal of Chemical Education. 63 (1): 57. Bibcode:1986JChEd..63...57C. doi:10.1021/ed063p57.
  9. ↑ Flory, P.J., "Principles of Polymer Chemistry" (1953)
  10. ↑ "ASTM D2765 - 16 Standard Test Methods for Determination of Gel Content and Swell Ratio of Crosslinked Ethylene Plastics". www.astm.org. Retrieved 1 April 2018.
  11. ↑ "ASTM F2214 - 16 Standard Test Method for In Situ Determination of Network Parameters of Crosslinked Ultra High Molecular Weight Polyethylene (UHMWPE)". www.astm.org. Retrieved 1 April 2018.
  12. ↑ Siddik, Zahid H. (2003). "Cisplatin: Mode of cytotoxic action and molecular basis of resistance". Oncogene. 22 (47): 7265–7279. doi: 10.1038/sj.onc.1206933 . PMID   14576837. S2CID   4350565.
  13. ↑ Noll, David M.; Mason, Tracey Mcgregor; Miller, Paul S. (2006). "Formation and Repair of Interstrand Cross-Links in DNA". Chemical Reviews. 106 (2): 277–301. doi:10.1021/cr040478b. PMC   2505341 . PMID   16464006.
  14. ↑ Christoe, John R.; Denning, Ron J.; Evans, David J.; Huson, Mickey G.; Jones, Leslie N.; Lamb, Peter R.; Millington, Keith R.; Phillips, David G.; Pierlot, Anthony P.; Rippon, John A.; Russell, Ian M. (2005). "Wool". Kirk-Othmer Encyclopedia of Chemical Technology. doi:10.1002/0471238961.2315151214012107.a01.pub2. ISBN   9780471484943.
  15. ↑ Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7.
  16. ↑ Prasad, Anand; Bekker, Peter; Tsimikas, Sotirios (2012-08-01). "Advanced glycation end products and diabetic cardiovascular disease". Cardiology in Review. 20 (4): 177–183. doi:10.1097/CRD.0b013e318244e57c. ISSN   1538-4683. PMID   22314141. S2CID   8471652.
  17. ↑ "Pierce Protein Biology - Thermo Fisher Scientific". www.piercenet.com. Retrieved 1 April 2018.
  18. ↑ Kou Qin; Chunmin Dong; Guangyu Wu; Nevin A Lambert (August 2011). "Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers". Nature Chemical Biology. 7 (11): 740–747. doi:10.1038/nchembio.642. PMC   3177959 . PMID   21873996.
  19. ↑ Mizsei, Réka; Li, Xiaolong; Chen, Wan-Na; Szabo, Monika; Wang, Jia-huai; Wagner, Gerhard; Reinherz, Ellis L.; Mallis, Robert J. (January 2021). "A general chemical crosslinking strategy for structural analyses of weakly interacting proteins applied to preTCR-pMHC complexes". Journal of Biological Chemistry. 296: 100255. doi: 10.1016/j.jbc.2021.100255 . ISSN   0021-9258. PMC   7948749 . PMID   33837736.
  20. 1 2 Fancy, David A.; Kodadek, Thomas (1999-05-25). "Chemistry for the analysis of protein–protein interactions: Rapid and efficient cross-linking triggered by long wavelength light". Proceedings of the National Academy of Sciences. 96 (11): 6020–6024. Bibcode:1999PNAS...96.6020F. doi: 10.1073/pnas.96.11.6020 . ISSN   0027-8424. PMC   26828 . PMID   10339534.
  21. ↑ Suchanek, Monika; Anna Radzikowska; Christoph Thiele (April 2005). "Photo-leucine and photo-methionine allow identification of protein–protein interactions in living cells". Nature Methods. 2 (4): 261–268. doi: 10.1038/nmeth752 . PMID   15782218.
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