Self-assembled monolayers that transduce enzymatic activities to electrical signals.

The development of chemical methods to control the interactions of materials with proteins, enzymes, and cells is important to fundamental studies in chemical biology and to many applications in biotechnology. A wide range of strategies for immobilizing ligands to materials now allows excellent control over ligand–receptor interactions at an interface. An emerging theme in this field aims to add dynamic control over ligand–receptor interactions to enable the design of active substrates that can manipulate, in real time, the interactions of proteins and cells with a surface. Okano and co-workers, for example, exploited the thermalphase transition of poly(N-isopropylacrylamide) films to demonstrate substrates that could reversibly modulate the adhesion of cells. Willner and co-workers developed a class of monolayer substrates in which the activities of immobilized ligands can be reversibly switched with light. We have developed electroactive substrates that allow discrete ligands to be switched on or off in response to electrical potentials. These advances have provided an unprecedented ability to study and manipulate the adhesion of cells. In this communication, we extend on these early reports by demonstrating an interface that can specifically translate biological activities to electrical signals. This example now establishes the basis for designing electroactive interfaces that not only manipulate but also respond to cellular activities. Our approach for transducing a biological activity to an electrical signal relies on the enzymatic conversion of a redoxinactive molecule to generate a redox-active product (Figure 1). By tethering the substrate molecule to an electrode, the redox-active product resulting from enzyme action can be efficiently detected. We implement this strategy with the enzyme cutinase and 4-hydroxyphenyl valerate as the substrate. Cutinase is a 22 kDa serine esterase that efficiently removes the acyl group from this substrate, to produce the redox-active hydroquinone. We prepared a self-assembled monolayer (SAM) containing an alkanethiolate terminated by a 4-hydroxyphenyl valerate moiety [8] , and a tri(ethylene glycol)-terminated alkanethiolate in a ratio of 1:2. We used MALDI-TOF mass spectrometry to establish that the interfacial enzymatic