Matrigel
Encyclopedia
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.
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
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
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
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
Vasculogenesis
Vasculogenesis is the process of blood vessel formation occurring by a de novo production of endothelial cells.-Process:Though similar to angiogenesis, the two are different in one aspect: The term angiogenesis denotes the formation of new blood vessels from pre-existing ones, whereas...
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
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
.
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
Angiogenesis inhibitor
An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels . Some angiogenesis inhibitors are a normal part of the body's control, some are administered as drugs, and some come from diet....
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
Xenotransplantation
Xenotransplantation , is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenografts or xenotransplants...
in rodents as part of a cancer drug discovery program (4). Matrigel is mixed with immortalized human cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
cells and the mixture is injected subcutaneously in immunodeficient mice
Nude mouse
A nude mouse is a laboratory mouse from a strain with a genetic mutation that causes a deteriorated or absent thymus, resulting in an inhibited immune system due to a greatly reduced number of T cells. The phenotype, or main outward appearance of the mouse is a lack of body hair, which gives it...
. 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
Laminin
Laminins are major proteins in the basal lamina , a protein network foundation for most cells and organs...
, entactin
Entactin
Entactin also known as nidogen-1 is a protein that in humans is encoded by the NID1 gene. Entactin is a component of the basement membrane alongside other components such as collagen type IV, proteoglycans , laminin and fibronectin.- Function :Entactin is a member of the nidogen family of basement...
, and collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
which present cultured cells with the adhesive peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
sequences that they would encounter in their natural environment (1). Also present are growth factors that promote differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
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
Embryonic stem cell
Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells...
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.
External links
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