Biologists have a new alternative to fickle protein gels for culturing cells in three dimensions: a polymer gel that not only supports cell growth but handily transforms from gel to liquid when the temperature drops for easy cell harvesting (Biomacromolecules 2015, DOI: 10.1021/acs.biomac.5b01266).
In a 2012 lecture in Coventry, England, George M. Whitesides of Harvard University challenged polymer chemists to come up with a synthetic replacement for animal-protein-based hydrogels such as Matrigel for growing cells in 3-D. Cells grown in a 3-D matrix better represent body tissues than flat cell cultures. Protein-based gels have poor batch-to-batch reproducibility, Whitesides said, and cell biologists need hydrogels that will produce the same cell-growing environment every time. Steven P. Armes of the University of Sheffield was in the audience. His group had just made synthetic temperature-responsive gels, which he realized might be a ready-made replacement for Matrigel.
After the lecture, Armes caught up with Whitesides, and they began a collaboration to explore if the new gels would support 3-D cell culture.
Armes’s gel is constructed from a diblock copolymer, a covalently linked chain of two separate polymers: poly(glycerol monomethacrylate) (PGMA) and poly(2-hydroxypropyl methacrylate) (PHPMA). PGMA is water soluble, and PHPMA is hydrophobic. In water, the hydrophobic sides of the chains cluster together to form shapes that differ depending on the temperature. At refrigerator temperature (4 °C), the copolymer forms spherical nanoparticles that stay suspended in the water. At and above room temperature (25 °C), the spheres fuse to form very long wormlike structures, which entangle to form a soft hydrogel. The change from warm gel to cool liquid is fully reversible.