Enzymatically Triggered Delivery of Proteins from Gel Biomaterials using Orthogonal Sortases

Abstract

Hydrogel biomaterials have proven useful in a variety of medical and basic life science applications, including as platforms for 3D cell culture and controlled drug delivery. User-defined specification over protein presentation within such gels represents an exciting manner to tune their biochemical properties and their downstream biological effects. Building upon click-polymerized poly(ethylene glycol)-based gels reported previously by our group, this work first demonstrates the application of evolved sortases to site-specifically modify full-length proteins with reactive handles for immobilization within biomaterials, and then to exogenously trigger protein release via orthogonal transpeptidase-catalyzed reactions. This strategy proves effective in dynamically controlling biochemical aspects of gel systems, providing exciting opportunities to model complex physiological processes in vitro.