February 2, 2002
Most of the cells in your body are attached to their environment via specialized coatings on the outer surface of each cell. These coatings contain molecules called cell-surface receptors that can stick to the network of molecules found outside the cell. The receptors hang on to this extracellular matrix, holding the cell in place and separating it from its neighbors. Without this attachment many cells cannot reproduce or perform vital tasks. Therefore, researchers working with living cells in the lab have to create special surfaces or substrates to which the surface receptors of the cell can attach.
Many different substrates have been designed to bond with specific ligands. Traditionally, the disadvantage of this process is that it is difficult to detach the cells once their ligands bond with the substrate. Typically, an enzyme is used to destroy the peptides that hold the ligands to the substrate. However, this procedure can cause unwanted damage to the cells.
At the University of Chicago Materials Center, Milan Mrksich and his research group have created a new type of substrate that may solve this problem. They have developed a substrate that releases the cells attached to it when an electric current is applied. These special surfaces are known as dynamic substrates since their properties can be changed during an experiment.
Their approach is based on a self-assembled monolayer (SAM) of alkane thiolate on gold (Figure 1) that allows the electroactive quinone component to attach to a ligand. The quinone ester undergoes reduction when an electrical potential is applied to the underlying gold substrate to create the hydroquinone. This component rapidly changes to become lactone and releases peptide ligand (Figure 1B, 3rd panel). The SAM depicted in Figure 1 can release the tripeptide Arg-Gly-Asp (RGD). This peptide is a ligand found within many extracellular matrix proteins and cells can readily attach to this peptide ligand via the cell-surface receptor known as integrin receptors. With this system, the application of an electrical potential results in the release of the RGD ligand and, therefore, of cells that are attached to the substrate.
These dynamic substrates demonstrate remarkable tunable adhesion behavior: in Figure 2A, the cells on the left half of the picture are attached to an ordinary RGD substrate while the ones on the right half are attached to a dynamic substrate.
After a potential is applied for four minutes (Figure 2B) the cells attached to the electroactive quinone/RGD are released.
This work shows great promise in applications such as drug discovery, the study of cell adhesion and migration, and biotechnology/biomaterials.
- Electroactive Monolayer Substrates that Selectively Release Adherent Cells Woon-Seok Yeo, Christian D. Hodneland and Milan Mrksich, ChemBioChem 2(2001) 590-593.
- Turning On Cell Migration with Electroactive Substrates Muhammad N. Yousaf, Benjamin T. Houseman and Milan Mrksich, Angew. Chem. Int. Ed. 40 (2001) 1093-1096.