Functional protein micropatterning for drug design and discovery.

INTRODUCTION: The past decade has witnessed tremendous progress in surface micropatterning techniques for generating arrays of various types of biomolecules. Multiplexed protein micropatterning has tremendous potential for drug discovery providing versatile means for high throughput assays required for target and lead identification as well as diagnostics and functional screening for personalized medicine. However, ensuring the functional integrity of proteins on surfaces has remained challenging, in particular in the case of membrane proteins, the most important class of drug targets. Yet, generic strategies to control functional organization of proteins into micropatterns are emerging. AREAS COVERED: This review includes an overview introducing the most common approaches for surface modification and functional protein immobilization. The authors present the key photo and soft lithography techniques with respect to compatibility with functional protein micropatterning and multiplexing capabilities. In the second part, the authors present the key applications of protein micropatterning techniques in drug discovery with a focus on membrane protein interactions and cellular signaling. EXPERT OPINION: With the growing importance of target discovery as well as protein-based therapeutics and personalized medicine, the application of protein arrays can play a fundamental role in drug discovery. Yet, important technical breakthroughs are still required for broad application of these approaches, which will include in vitro "copying" of proteins from cDNA arrays into micropatterns, direct protein capturing from single cells as well as protein microarrays in living cells.