Matrigel

For citing references in Wikipedia, see Wikipedia:Citing sources.

Matrigel is the trade name for a gelatinous protein mixture secreted by Engelbreth-Holm-Swarm (EHS) mouse sarcoma cells and marketed by BD Biosciences and by Trevigen Inc under the name Cultrex BME. This mixture resembles the complex extracellular environment found in many tissues and is used by cell biologists as a substrate for cell culture (1,2).

A common laboratory procedure is to dispense small volumes of chilled (4°C) Matrigel onto plastic tissue culture labware. When incubated at 37°C (body temperature) the Matrigel proteins self-assemble producing a thin film that covers the surface of the labware.

Cells cultured on Matrigel demonstrate complex cellular behavior that is otherwise difficult to observe under laboratory conditions. For example, endothelial cells create intricate spiderweb-like networks on Matrigel coated surfaces but not on plastic surfaces (3). Such networks are highly suggestive of the microvascular capillary systems that suffuse living tissues with blood. Hence, the process by which endothelial cells construct such networks is of great interest to biological researchers and Matrigel allows them to observe this.

In some instances researchers may prefer to use greater volumes of Matrigel to produce thick three-dimensional gels. The utility of thick gels is that they induce cells to migrate from the surface to the interior of the gel. This migratory behavior is studied by researchers as a model of tumor cell metastasis.

Pharmaceutical scientists use Matrigel to screen drug molecules. A typical experiment consists of adding a test molecule to Matrigel and observing cellular behavior. Test molecules that promote endothelial cell network formation are candidates for tissue regeneration therapies whereas test molecules that inhibit endothelial cell network formation are candidates for anti-cancer therapies. Likewise, test molecules that inhibit tumor cell migration may also have potential as anti-cancer drugs. Matrigel is also commonly used to prepare human tumor xenografts in rodents as part of a cancer drug discovery program (4). Matrigel is mixed with immortalized human cancer cells and the mixture is injected subcutaneously in immunodeficient mice. A human tumor usually forms in two to four weeks. This model system allows a researcher to test an anti-cancer compound in a surrogate host.

The ability of Matrigel to stimulate complex cell behavior is a consequence of its heterogeneous composition. The chief components of Matrigel are structural proteins such as laminin, entactin, and collagen which present cultured cells with the adhesive peptide sequences that they would encounter in their natural environment (1). Also present are growth factors that promote differentiation and proliferation of many cell types. Matrigel contains numerous other proteins in small amounts and its exact composition is can vary from lot to lot. For this reason, Matrigel may not be appropriate for experiments which require a precise knowledge of all proteins and concentrations.

Matrigel is also used as an attachment substrate in embryonic stem cell culture (5). When embryonic stem cells are grown in the absence of feeder cells, extracellular matrix components such as diluted Matrigel are necessary to maintain the pluripotent, undifferentiated state (self-renewal). When used undiluted, Matrigel will promote stem cell growth and differentiation.

References

1. Hughes, C.S., Postovit, L.M., Lajoie, G.A. Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteonomics 10:1886-1890, 2010. 2. Benton, G., George, J., Kleinman, H.K., Arnaoutova, I. Advancing science and technology via 3D culture on basement membrane matrix. J. Cellul. Physiol., 221:18-25, 2009. 3. Arnaoutova, I., George, J., Kleinman, H.K., and Benton, G. The endothelial cell tube formation assay on basement membrane turns 20. Angiogenesis, 12:267-274, 2009. 4. Benton, G., Kleinman, H.K., George, J., Arnaoutova, I. Multiple uses of basement membrane-like matrix (BME/Matrigel) in vitro and in vivo with tumor cells. International J. Cancer 128:1751-1757, 2011. 5. Xu, C., Inokuma, M.S., Denham, J., Golds, K., Kundu, P., Gold, J.D., Carpenter, M.K. feeder-free growth of undifferentiated human embryonic stem cells. Nat. Biotechnol. 19: 971-974, 2001.

External links

• BD Biosciences

http://www.trevigen.com Sem Cancer.2005.05.004

Review Matrigel: Basement membrane matrix with biological activity

Hynda K. Kleinman and George R. Martin NIDCR, NIH