Electrochemically Directed Assembly of Designer Coiled-Coil Telechelic Proteins

We report the design and characterization of a de novo electrogelation protein comprising a central spider silk glue motif flanked by terminal pH-triggered coiled-coil domains. The coiled-coiled domains were designed to form intramolecular helix bundles below a sharply defined pH-trigger point (∼pH 5.3), whereas the spider silk glue protein, because of its substantial Glu content, serves both as an anionic electrophoretic transport element at neutral and elevated pH and as a disordered linker chain between the associated helix bundles at reduced pH. We show that in an electrochemical cell, a solution of these telechelic proteins migrates toward the anode where the terminal coiled-coil domains are triggered to form coiled-coil assemblies that act as transient cross-links for the <i>e</i>-gel state. Upon cessation of the current, the coiled-coil domains become denatured and the <i>e</i>-gel transforms back into a fluid solution of polypeptides in a fully reversible manner. This simplified triblock protein design mimics many of the characteristics of more complex electrogelation proteins, such as silk fibroin. As such, it provides some insight into possible general mechanisms of protein electrogelation. Moreover, this general class of electrogelation proteins has the potential for biomedical applications of electrochemically triggered gelation, such as externally switchable delivery of therapeutic cell and drugs from a responsive matrix.