Matrices for 3D Cell Culture

A variety of matrices are currently being used for culturing cells in a 3D environment, including a wide range of natural proteins to synthetic scaffolds. The choice of a suitable matrix strongly depends on the cell type being used and specific experimental questions. Hydrogels, such as collagen and fibrin, are water-swollen polymer networks that are commonly used. They can substitute the natural matrix in 3D cell culture experiments because they mimic several key features of the native extracellular matrix (ECM).

Collagen I is the main component of connective tissue and is abundant in the mammalian body. The fibrous protein consists of three α-chains that combine to create a rope-like triple helix, thus providing tensile strength to the ECM. The triple helices aggregate and form fibrils in a self-organized manner. In vivo, the fibrils gelate into fibers to form tissue such as tendons or dermis.

Collagen (mostly type I) is widely used in 3D cell culture for modeling the extracellular matrix. To embed the cells in the matrix, they are mixed with the liquid gel and pipetted into the vessel. Raising the pH and temperature leads to self-assembly of the collagen fibrils, which results in gelation and the encapsulation of the cells.

Matrigel^® is a collagen- and laminin-containing hydrogel used in many 3D cell culture approaches (e.g., organoid culture). It is derived from Engelbreth–Holm–Swarm (EHS) mouse sarcoma tumors and consists mainly of laminin, type IV collagen, and entactin.

Detailed comparison of hydrogels, including their applications, advantages, and disadvantages:

Caliari SR, Burdick JA (2016) A practical guide to hydrogels for cell culture. Nat Methods 13(5):405–414. 10.1038/nmeth.3839
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The structure of collagen.