A self-assembled Fmoc-peptide hydrogel has been interfaced with a liquid crystal (LC) display to give an optical sensor for enzyme activity. An Fmoc-TL-OMe hydrogel was selected as it can be formed in situ by enzyme-mediated assembly with thermolysin, and undergoes enzyme-mediated diassembly upon subtilisin addition. This enzyme-responsive hydrogel provides a semi-rigid, highly hydrated and biocompatible environment that also holds the LC display in place. A dual layer design was developed, where a phospholipid-loaded upper gel layer was separated from the LC display by a phospholipid free lower layer. Subtilisin (0.15 mM) digested both layers to give a gel-to-sol transition after several hours that liberated the phospholipid and produced a light-to-dark optical change in the LC display. The optical response was dependent upon the gel-to-sol transition; elastase or common components of serum did not disassemble the Fmoc-TL-OMe hydrogel and did not give an optical response. ; Times Cited: 0 0