The University of Chicago   The Mrksich Laboratory



Dynamic Substrates

Our group has developed an innovative approach to developing substrates that are dynamic and that can switch the activities of immobilized ligands in situ.54 These dynamic substrates offer an unprecedented opportunity to understand the responses of adherent cells to changes in the ECM; including, for example, changes caused by binding of proteins to matrix, proteolytic action on matrix, and cellular forces that unfold matrix proteins. The approach takes advantage of the presence of the gold film underlying the monolayer, and the use of applied electrical potentials to effect electrochemical conversions of the monolayer. We have designed a series of monolayers that respond to these applied potentials by revealing or releasing ligands at the interface, and therefore for changing the ECM ligands with which an adherent cell interacts.50, 57, 79, 85 We demonstrated the use of these dynamic substrates for studies of cell migration and for patterning multiple cell types into defined cocultures.52, 58

Dynamic Substrates
Figure 4.  Design of substrates that can turn on cell migration and growth. (A) Monolayers that present hydroquinone groups mixed with penta(ethylene glycol) groups are inert to cell attachment. Electrochemical oxidation converts the hydroquinone groups to quinone groups, which then undergo Diels-Alder reaction with a diene-Arg-Gly-Asp conjugate (RGD-Cp) to introduce the peptide onto the surface. The resulting monolayers support the attachment and spreading of cells. Cells attached only to the protein-coated regions (B), but after oxidation of the substrate in the presence of RGD-Cp, cells were able to migrate and then grow to fill the entire monolayer (C).