Chang Douglas H, Wang Fengrui, Palecek Sean P, Lynn David M
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Dr., Madison, Wisconsin 53706, United States.
Department of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, Wisconsin 53706, United States.
ACS Appl Mater Interfaces. 2025 May 14;17(19):27882-27894. doi: 10.1021/acsami.5c02541. Epub 2025 May 2.
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.
我们报道了一种注入液晶的“光滑”液体注入多孔表面（LC-SLIPS）的设计，该表面能够实现裸眼检测，并报告水性介质中肽和蛋白酶的结构差异及活性。我们证明，与LC-SLIPS接触的小体积（如20微升）水溶液液滴会表现出滑动行为，其显著变化取决于溶解在其中的模型两亲性β-肽和α/β-肽的浓度、结构及物理化学性质（如疏水性）。这些滑动时间的巨大差异使得能够裸眼检测和区分肽结构的变化，包括与肽两亲性差异相关的侧链取代、端基结构、主链结构和电荷。我们进一步证明，LC-SLIPS可用于监测其他生化过程，包括蛋白酶的消化作用，这些过程会影响两亲性肽的结构变化，因此可用于开发能够灵敏报告酶活性的新型裸眼检测方法。作为概念验证，我们表明，由模型肽降解导致的液滴滑动的大幅度且肉眼可见的变化，可用于检测水溶液中低至12.5纳克/毫升的胰蛋白酶。该结果进而成为基于LC-SLIPS的检测方法的基础，该方法可用于检测合成尿液样本中临床相关浓度（25至25,000纳克/毫升）的胰蛋白酶原，胰蛋白酶原是急性胰腺炎的一种成熟生物标志物。这种“滑动”检测方法在概念上很简单，仅需肉眼监测和/或手持秒表进行读数，凸显了其在低成本即时诊断应用方面的潜力。总体而言，我们的结果证明了LC-SLIPS能够捕捉和报告与两亲性肽的其他治疗特性及应用相关的结构信息，这在药物设计和筛选方面也可能有用。
