Slippery Liquid-Infused Porous Surfaces Infused with Thermotropic Liquid Crystals Enable Droplet-Based, Naked-Eye Reporting of Changes in Peptide Structure and Protease Activity

We report the design of liquid crystal-infused "slippery" liquid-infused porous surfaces (LC-SLIPS) that permit naked-eye detection and reporting on the structural differences and activities of peptides and protease enzymes in aqueous media. We demonstrate that small (e.g., 20 μL) droplets of aqueous solutions placed in contact with LC-SLIPS exhibit sliding behaviors that vary substantially with the concentrations, structures, and physicochemical properties (e.g., hydrophobicity) of model amphiphilic β- and α/β-peptides dissolved within them. These large differences in sliding times permit naked-eye detection and discrimination of changes in peptide structure, including side-chain substitution, end group structure, backbone structure, and charge that correlate with differences in peptide amphiphilicity. We demonstrate further that LC-SLIPS can be used to monitor other biochemical processes, including digestion by proteases, that affect changes in the structures of amphiphilic peptides and can, thus, be used to develop novel, naked-eye assays that can report sensitively on enzymatic activity. As proof of concept, we show that large and visually observable changes in droplet sliding resulting from the degradation of a model peptide can be used to detect the presence of trypsin in aqueous solutions at levels as low as 12.5 ng/mL. That result, in turn, served as the basis of an LC-SLIPS-based assay that can be used to detect clinically relevant concentrations (from 25 to 25,000 ng/mL) of trypsinogen, a well-established biomarker for acute pancreatitis, in samples of synthetic urine. This "sliding" assay is conceptually straightforward and requires only visual monitoring and/or a hand-held stopwatch for readout, highlighting the potential for low-cost, point-of-care diagnostics applications. Overall, our results demonstrate the ability of LC-SLIPS to capture and report structural information relevant to other therapeutic properties and applications of amphiphilic peptides that could also be useful in the context of drug design and screening.