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Cross-links are covalent bonds linking one polymer chain to another. They are the characteristic property of thermosetting polymer materials. In biology, cross-linking has applications in forming polyacrylamide gels for gel electrophoresis and in protein studies. Crosslinking inhibits close packing of the polymer chains, preventing the formation of crystalline regions. The restricted molecular mobility of a crosslinked structure limits the extension of the polymer material under loading.

Cross-links are formed by chemical reactions that are initiated by heat and/or pressure, or by the mixing of an unpolymerized or partially polymerized resin with specific chemicals called crosslinking reagents. Cross-linking can be induced in materials that are normally thermoplastic through exposure to radiation.

In most cases, cross-linking is irreversible, and the resulting thermosetting material will degrade or burn if heated, without melting. Once a substance is cross-linked, the product is very hard or impossible to recycle. In some cases, though, if the cross-link bonds are sufficiently different, chemically, from the bonds forming the polymers, the process can be reversed. Permanent wave solutions, for example, break and re-form naturally occurring cross-links (disulfide bonds) between protein chains in hair.

The chemical process of vulcanization is a type of cross-linking and it changes the property of rubber to the hard, durable material we associate with car and bike tires. This process is often called sulphur curing, and the term vulcanization comes from Vulcan, the Roman god of fire. However, this is a slow process, taking around 8 hours. A typical car tire is cured for 15 minutes at 150°C. However, the time can be reduced by the addition of accelerators such as 2-benzothiazolethiol or tetramethylthiuram disulphide. Both of these contain a sulphur atom in the molecule that initiates the reaction of the sulphur chains with the rubber. Accelerators increase the rate of cure by catalysing the addition of sulphur chains to the rubber molecules.

Cross-links can be made also by purely physical means. For example, electron beams are used to cross-link the C type of cross-linked polyethylene. Other types of cross-linked polyethylene are made by addition of peroxide during extruding (type A) or by addition of a cross-linking agent (eg. vinylsilane) and a catalyst during extruding and then performing a post-extrusion curing.


Crosslinker use in protein study

A variety of crosslinkers are used to analyze subunit structure of proteins, protein interactions and various parameters of protein function. Subunit structure is deduced since crosslinkers only bind surface amino residues in relatively close proximity in the native state. Protein interactions are often too weak or transient to be easily detected, but by crosslinking, the interactions can be captured and analyzed.

Examples of some common crosslinkers are the imidoester crosslinker dimethyl suberimidate, the NHS-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 caboxyls into amine-reactive isourea intermediates that bind to lysine residues or other available primary amines.

In-vivo crosslinking of protein complexes using photo-reactive amino acid analogs was introduced in 2005 by researchers from the Max Planck Institute [1] In this method, 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 angstroms of the photo-reactive amino acid analog.

Crosslinker for keratoconus treatment

Cross linking by means of photosensitizers (Riboflavin) and UV light has entered clinical application for the treatment of keratoconus [1]. Keratoconus is a disease of the cornea that makes the cornea become weak and may gradually bulge outward. Approximately half of the keratoconus patients have significant visual problems beyond corrective lenses. The only resolution to keratoconus has been corneal transplantation, with a long healing period and unpredictable refractive error. Today, Corneal Cross Linking is used to increase the biomechanical stability of cornea to avoid corneal transplantation.

See also


  1. ^ Suchanek, M., Radzikowska, A., and Thiele, C. (2005) Photo-leucine and photo-methionine allow identification of protein-protein interactions in living cells. Nature Methods. 2, 261 – 268.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Cross-link". A list of authors is available in Wikipedia.
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