Biofriendly Sol–Gel Processing for the Entrapment of Soluble and Membrane-Bound Proteins: Toward Novel Solid-Phase Assays for High-Throughput Screening

The last decade has seen a revolution in the area of sol-gel-derived biomaterials since the demonstration that these materials can be used to encapsulate biological species such as enzymes, antibodies, and other proteins in a functional state. In particular, recent years have seen tremendous progress in the development of more "protein-friendly" sol-gel processing methods and their use for immobilization of delicate proteins, including key drug targets such as kinases and membrane-bound receptors. The latter example is particularly impressive, given the inherently low stability of membrane receptors and the need to stabilize an amphiphilic bilayer lipid membrane to maintain receptor function. In this Account, we provide an overview of the advances in biofriendly sol-gel processing methods developed in our research group and others and highlight recent accomplishments in the immobilization of both soluble and membrane-bound proteins, with particular emphasis on enzymes and membrane receptors that are drug targets. Emerging applications of sol-gel-entrapped proteins, focusing on the development platforms for high-throughput screening of small molecules, are also described.